Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the results of a study based on an animal model concurring whether captopril can improve microcirculation in the small intestine in nonocclusive mesenteric ischemia dependent on when therapy is begun. Cardiogenic shock was produced by pericardial tamponade with starch solution. The flow in the carotid artery could be reduced to 43% of the preshock value. In four therapy groups and a control group the intestinal microcirculation was examined by laser Doppler flowmetry in the serosa and mucosa. The measurements were taken at regular intervals during the 4 h of the experiments. Captopril was either given systemically or locoregionally through the upper mesenteric artery. Therapy was given at the beginning of the shock or 1 h after induction of shock at a dosage of 0.25 mg/kg body weight as a bolus and continuous application of 10 micrograms/kg body wt. Concerning the hemodynamic changes during shock the group receiving captopril systemically at the beginning of shock showed a significant (P = 0.05) improvement in microcirculation compared to the controls and other therapy groups. Flow reduction was seen in the controls (156-32 relative flow units = RFU) in group Ia (systemic therapy 1 h after shock), as well as the controls (129 to 12 RFU) and, in group Ib (systemic therapy beginning with shock) a flow rise could be seen (307 to 481 RFU). In group IIa (local therapy 1 h after shock) (a steady flow was seen (168-170 RFU) and in group IIb (local therapy beginning with shock) and group Ib an increase in flow was also measured (226-303 RFU). This positive effect of captopril on the intestinal perfusion was observed when applied 1 h after the induction of shock.
 ...
PMID:[Significance of therapy timing for the effects of systemic and local therapy with the ACE inhibitor captopril on intestinal microcirculation in manifest mesenteric ischemia. An animal experiment study in the swine]. 750 Jul 99

Endothelial cells modulate the tone of the underlying smooth muscle by generating endothelium-derived relaxing and constricting factors. Captopril (CPT), unlike other angiotensin-converting enzyme (ACE) inhibitors, contains a sulfhydryl (-SH) group and can act as a free radical scavenger. Iloprost (ILO) is a synthetic analogue of prostacyclin and mimics the effects of this compound. This study was designed to investigate the effect of ILO and CPT on the mechanism of endothelin (ET) release after mesenteric ischemia-reperfusion (I/R) injury in the rat. Sprague-Dawley rats were divided into five groups: sham-operated, control, ILO (25 micrograms/kg), CPT (10 micrograms/kg), and ILO + CPT. The superior mesenteric artery was occluded for 30 min and then allowed 90 min of reperfusion, except in the sham-operated group, and the corresponding agents were given to the treated groups prior to I/R injury. After I/R injury, portal venous blood was obtained for ET assay, and ileal tissue samples were also obtained for the determination of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) and for histopathological examination. MDA levels were significantly lower in the CPT, ILO and, ILO + CPT groups than in the control group, indicating the inhibition of lipid peroxidation in all groups. ET levels increased in the control group, and this increase was reversed with ILO. In the CPT group, ET levels were significantly increased, and the addition of ILO did not affect this increase. Significant cytopreservative effect was achieved with ILO and CPT, the latter being more prominent histopathologically. CPT exerts a significant protective effect on the intestinal mucosa after I/R injury. This protection is accomplished by increased ET levels and seems to be unrelated to its inhibitory effect on lipid peroxidation and also unrelated to the arachidonic acid cascade.
 ...
PMID:Captopril increases endothelin serum concentrations and preserves intestinal mucosa after mesenteric ischemia-reperfusion injury. 753 37

This study was designed to examine if acute systemic blockade of nitric oxide (NO) production by inhibition of nitric oxide synthase (NOS) with N-omega-nitro-L-arginine methyl ester (L-NAME) would worsen the severity of ischemic acute renal failure (ARF). Initially three groups of rats, were studied: 45 min of bilateral renal ischemia (I) alone, Group I; L-NAME (L; 10 mg/kg BW, i.v.) alone, Group L; and L-NAME administered 15 min before renal ischemia, Group L+I. We observed, however, a 60% mortality in Group I+L during the first 4 h of reflow. Captopril, administered acutely 15 min before L-NAME in an attempt to offset any detrimental effects of increased angiotensin II generation in response to renal ischemia, failed to obviate the mortality because 67% of rats in this group (Group C+L+I) also died. Therefore, additional studies were performed in rats instrumented for cardiovascular studies to evaluate the acute hemodynamic responses during the first 90 min of reperfusion following renal ischemia in rats pretreated with L-NAME. As expected, L-NAME injection was accompanied by a 25-30 mm Hg increase in mean systemic arterial pressure (SAP) (p < 0.05), a bradycardia (p < 0.02), and a decrease in cardiac output (CO) (p < 0.02). The increase in SAP was due exclusively to an increase in systemic vascular resistance (SVR) (p < 0.01). Ischemia and reflow in the L-NAME-treated rats were attended by a progressive increase in SVR and a progressive decrease in CO such that by the end of 45 min of reperfusion SVR had increased 10-fold and CO had decreased to one third of its initial rate (both p < 0.02). Pulmonary artery pressure (PAP) increased promptly following L-NAME injection. Total pulmonary resistance (PRT) increased significantly by the end of reperfusion. L-NAME in combination with renal ischemia and reflow induces a large increase in both SVR and PRT, and is accompanied by a 70% reduction in CO and substantial mortality.
 ...
PMID:Nitric oxide synthase inhibition and acute renal ischemia: effect on systemic hemodynamics and mortality. 756 11

A double-blind, placebo-controlled, crossover study was carried out to evaluate the short-term effects of captopril on exercise tolerance in 18 normotensive patients with chronic stable angina pectoris and normal left ventricular function. Captopril 25 mg (or placebo) was given twice, i.e. in the evening (10 p.m.) and the following morning (8 a.m.), prior to a maximal symptom-limited bicycle exercise test (11 a.m.). Captopril reduced the systolic and diastolic blood pressures at rest (p < 0.01) without causing any reflex tachycardia. The time to onset of S-T depression was prolonged (p < 0.05), and the maximal S-T depression was reduced (p < 0.02). No differences were found between captopril and placebo in total exercise duration or time to onset of angina. The effects of captopril on exercise-induced ischemia were demonstrated most clearly in patients who responded with a greater than 10 mm Hg fall in the resting systolic blood pressure. In conclusion, this study suggests that captopril has anti-ischemic properties, which may be of importance in the treatment of patients with chronic stable angina and normal left ventricular function. These beneficial effects probably relate to a reduction in afterload and myocardial wall stress and therefore a reduction in myocardial oxygen demand.
 ...
PMID:Short-term effects of captopril on exercise tolerance in patients with chronic stable angina pectoris and normal left ventricular function. 758 53

Hearts with pressure-overload hypertrophy show an increased intracardiac activation of the renin-angiotensin system (RAS) which may contribute to myocardial ischemia and reperfusion injury. This study investigates whether the hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury and whether the specific inhibition of the cardiac RAS by captopril would modify ischemia and reperfusion injury in the hypertrophied myocardium. By using the isolated working rat heart model, hypertrophied hearts, induced by abdominal aortic banding for 6 weeks, were subjected to 120 min of hypothermic ischemic arrest followed by 30 min of reperfusion. The postischemic cardiac function recovery was measured in both the untreated (n = 10) and the captopril-treated (n = 11) groups and was compared with that of the sham-operated non-hypertrophied control hearts (n = 10). Captopril (23.0 microM) was given to one group with the hypertrophied hearts from the beginning of ischemia to the end of reperfusion. In comparison with the normal control hearts, the cardiac function recovery after 30 min reperfusion was poorer in the hypertrophied hearts, which was associated with a lower recovery of coronary flow (CF), a higher myocardial lactate content and a retarded peak myocardial creatinkinase (CK) release. Captopril significantly improved the cardiac function recovery, which was associated with an increased CF recovery and a lower myocardial lactate content, and a rapid peak CK release. In conclusion, this study shows that the hypertrophied myocardium leads to an increased susceptibility to ischemia and reperfusion injury. Captopril, most likely by its inhibition of the cardiac RAS, is effective in preventing the ischemia and reperfusion injury in the hypertrophied heart.
 ...
PMID:Captopril cardioplegia on myocardial protection in the hypertrophied rat hearts. 772 80

Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. NADH and ADP (not NAD+ or ATP) enhanced LADH inactivation by Cu(II). NADH also enhanced the effect of Cu(II)/H2O2. Dihydrolipoamide, dihydrolipoic acid, Captopril, acetylcysteine, EDTA, DETAPAC, histidine, bathocuproine, GSSG and trypanothione prevented LADH inactivation. 100 microM GSH, DL-dithiothreitol, N-(2-mercaptopropionylglicine) and penicillamine protected LADH against Cu(II)/Asc and Cu(II), whereas 1.0 mm GSH and DL-dithiothreitol also protected LADH against Cu(II)/H2O2. Allopurinol provided partial protection against Cu(II)/H2O2. Ethanol, mannitol, Na benzoate and superoxide dismutase failed to prevent LADH inactivation by Cu(II)/H2O2 or Cu(II). Catalase (native or denaturated) and bovine serum albumin protected LADH but that protection should be due to Cu binding. LADH inhibited deoxyribose oxidation and benzoate hydroxylation by Cu(II)/H2O2. It is concluded that site-specifically generated HO, radicals were responsible for LADH inactivation by Cu(II) Fenton systems. The latter effect is discussed in the context of ischemia-reoxygenation myocardial injury.
 ...
PMID:Inactivation of heart dihydrolipoamide dehydrogenase by copper Fenton systems. Effect of thiol compounds and metal chelators. 775

The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation and increase prostacyclin and bradykinin levels. In the chronic phase remodelling may be attenuated. At present, a large number of controlled clinical trials mainly focussing on the effects of ACE-inhibition in the chronic phase is under way. Only few studies concentrate on the effect of acute intervention with ACE-inhibitors in ischemia-reperfusion i.e. thrombolysis in myocardial infarction. In the Captopril And Thrombolysis pilot study (CAT pilot-study) 3 mg and 6.25 mg captopril was tolerated well as adjunctive therapy to intravenous streptokinase. Decrease in mean arterial blood pressure (36 +/- 11%) after 6.25 mg was comparable to the control group (30 +/- 7%). Furthermore noradrenaline levels decreased dose dependently to 47 +/- 6 and 38 +/- 7% from baseline respectively. These results prompted a large nationwide acute intervention trial with captopril in 300 patients receiving thrombolytic therapy: the Captopril And Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring and neurohumoral measurements immediately upon thrombolysis and during the first year after myocardial infarction. Blinded data show a favourable blood pressure response, with systolic hypotension below 100 mm Hg occurring only in 0.2% of patients.
 ...
PMID:Angiotensin-converting enzyme inhibition during thrombolytic therapy in acute myocardial infarction: the Captopril and Thrombolysis Study (CATS). 812 21

The clearance of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine provide a measure of effective renal plasma flow, yet these clearances are proportional to renal plasma flow only if the extraction fraction remains constant. To determine the effect of unilateral renal artery stenosis, captopril, renal ischemia, and partial renal vein occlusion on renal blood flow and the extraction fraction of [131I]orthoiodohippurate, 99mTc-mercaptoacetyltriglycine, and [125I]iothalamate, we conducted a series of constant infusion studies in Sprague-Dawley rats. Renal artery flow reduction of approximately 70% decreased the extraction fraction of all three agents (P < or = .05). Captopril had no effect on extraction fraction in controls, but it produced a further decrease in extraction fraction of 99mTc-mercaptoacetyltriglycine and [131I]orthoiodohippurate in rats with renal artery stenosis (P < or = .05). Ischemia resulted in a 16% decrease in flow (P < .01) but a much larger (47% to 65%) decrease in extraction fraction of all three agents (P < .002). Partial renal vein occlusion also decreased the extraction fraction of all three agents (P < or = .05). The changes in extraction fraction imply that the clearances of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine in disease states may not be proportional to renal plasma flow. Furthermore, in rats with renal artery stenosis it appears that renal blood flow must fall below a critical threshold of approximately 58% before extraction fraction decreases; as renal blood flow is further reduced below this threshold, there is a corresponding reduction in extraction fraction (P < .01).
 ...
PMID:Renal artery stenosis and ischemia. Effect on renal blood flow and extraction fraction. 828 36

Coronary artery occlusion results in the acute activation of the renin-angiotensin system and production of angiotensin II, a potent vasoconstrictor and positive inotropic agent. This has raised the possibility that angiotensin converting enzyme (ACE) inhibitors might be "cardioprotective" (that is, might attenuate myocardial injury, dysfunction and necrosis) in the setting of acute ischemia and infarction. Captopril, enalapril and ramipril have, in fact, been reported to acutely limit myocardial injury and necrosis in models of permanent coronary artery occlusion. The mechanisms responsible for this cardioprotection are complex, but include favorable alterations in myocardial oxygen supply/demand, and, in some instances, inhibition of bradykinin metabolism and/or increased prostaglandin synthesis. Other studies, however, have failed to document a reduction in infarct size with ACE inhibitor treatment. Results obtained in models of coronary occlusion/reperfusion have also been mixed. In models of brief transient ischemia not associated with necrosis, captopril and zofenopril have consistently been found to attenuate postischemic contractile dysfunction of the viable but "stunned" myocardium during the early hours following relief of ischemia. In contrast, there is no consensus on the effects of enalapril on the stunned myocardium: both positive and negative results have been obtained. Similar disparity has been reported in models of more prolonged ischemia/reperfusion resulting in subendocardial necrosis: some studies have reported myocardial salvage, while others have provided disturbing evidence of apparent exacerbation of myocardial necrosis with captopril and enalapril therapy. Thus, after a decade of investigative effort, the question of whether ACE inhibitors are "cardioprotective" in the setting of acute myocardial ischemia and infarction remains unresolved. Nonetheless, clinical protocols are in progress to assess the effects of early ACE inhibitor treatment in patients with acute myocardial infarction.
 ...
PMID:"Cardioprotection" by ACE-inhibitors in acute myocardial ischemia and infarction? 835 29

Myocardial infarction induced hypertrophy of non-infarcted myocardium, in parallel with interstitial and perivascular fibrosis and a decreased capillary density, could increase sensitivity to ischemia. The structural cardiac changes can be reversed by long-term captopril treatment. In the present study, ischemic sensitivity in relation to cardiac perfusion was studied in isolated, perfused hearts of untreated and captopril-treated infarcted rats. In chronically (8 weeks) infarcted hearts, maximal vasodilation in response to administered adenosine and nitroprusside, as well as to endogenously released vasodilators during reperfusion, was decreased, suggesting impaired cardiac perfusion. Ischemic release of purines and lactate was reduced in infarcted hearts, indicating decreased sensitivity to ischemia of the remodeled myocardium. Captopril treatment (3-8 weeks post myocardial infarction), which reversed hypertrophy without affecting the flow capacity of the coronary vascular bed, restored maximal cardiac perfusion. Ischemic ATP breakdown was not affected by captopril, whereas lactate release was even further reduced, suggesting alterations towards a more aerobic ATP production. These data indicate that despite the reduced maximal cardiac perfusion, the remodeled myocardium of infarcted hearts is less sensitive to ischemia. Reversal of hypertrophy by chronic captopril restored maximal cardiac perfusion and led to a better preservation of aerobic ATP production during ischemia.
 ...
PMID:Sensitivity to ischemia of chronically infarcted rat hearts; effects of long-term captopril treatment. 886 98


<< Previous 1 2 3 4 5 Next >>