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

Exogenous bradykinin was administered to pigs in which an experimental infarction was evoked by ischemia and reperfusion. Ischemia (45 min) was induced in a closed-chest model with a balloon catheter in the left anterior descending artery, reperfusion by deflating and removing the balloon. The pigs were treated with saline (n = 11) or bradykinin (0.1 mg/kg in 30 min) infusion (n = 10) during the last 15 min of the ischemic period and the first 15 min of reperfusion. During ischemia, heart rate increased in the saline group to 120 +/- 9% of the initial value (p less than 0.05) and in the bradykinin group to 155 +/- 13% (p less than 0.05). After reperfusion, the rate-pressure product was increased in both groups. The increase of arterial creatine kinase levels was significantly less in the bradykinin-treated group. However, the catecholamine and purine levels were increased, as was the plasma renin activity when compared with the saline group. Two weeks after the infarction, six pigs had died in each group. In three out of five surviving saline-treated pigs and one out of four surviving bradykinin-treated pigs, a sustained ventricular tachyarrhythmia was inducible after programmed electrical stimulation. In conclusion, although systemically administered bradykinin caused a temporary increase in myocardial ischemia, it did reduce the (enzymatic indices of) infarct size. Therefore, the beneficial effects, previously found for ACE-inhibitors might at least partially be related to the potentiation of endogenous bradykinin.
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PMID:Beneficial effects of bradykinin on porcine ischemic myocardium. 187 66

It was demonstrated recently that a local renin-angiotensin system (RAS) exists in the heart and coronary vessels, and the angiotensin converting enzyme inhibitors can protect the heart from ischemia. Eight patients with NYHA class II-IV subjected to valve replacement were studied in protecting the heart from global ischemia with captopril during open heart surgery. After the ascending aorta was clamped, 500-1000 ml 4 degrees C modified St. Thomas No 1 cardioplegic solution containing 0.058-0.23 mmol/L captopril was perfused into coronary arteries under pressure until the electrocardiogram showed disappearance of myocardial electroactivity. The cardioplegic perfusion was repeated every 30 minutes thereafter during cardiopulmonary bypass (CPB). All the hearts rebeat after reperfusion either spontaneously or from defibrillation without any trouble. Three patients developed an A-V dissociation which returned to sinus rhythm or atrial fibrillation after a tiny dose of dopamine or isoprenaline intravenously. All the patients weaned from the CPB easily with a stable heart rate and a reasonable MAP. None of them needed inotropic support, even those with severe heart failure before operation did not either, and all recovered uneventfully.
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PMID:Captopril as a component of cardioplegia in protecting the myocardium from global ischemia during open heart surgery. A preliminary clinical report. 187 3

Recovery from renal ischemia requires regeneration of damaged tubular epithelium. Previous studies have examined the expression of proto-oncogenes and growth factors after ischemia, but the response of genes coding for structural and functional genes has not been scrutinized. Rats were subjected to 40 minutes of renal artery occlusion and 60 minutes to 96 hours of reperfusion. Total RNA was isolated and mRNA for the structural protein actin, the enzymes superoxide dismutase and renin, the proto-oncogene c-fos, the nuclear protein histone H2b, and the putative marker for cell injury TRPM-2 was quantitated by Northern hybridization. Expression of the proto-oncogene c-fos was seen early but for only short duration. Histone gene expression was not markedly increased until 24 hours after ischemia, but remained increased for several days. Renin mRNA was undetectable one hour after ischemia, but was present in normal amounts at 24 and 48 hours. In contrast, superoxide dismutase mRNA was present in decreased amounts 24, 48, and 96 hours after ischemia. TRPM-2 gene expression was greatly increased 24 to 72 hours after ischemia and began decreasing at 96 hours. This selective sequence of gene expression or repression after renal ischemia might maximize the proliferative repair process. This information will be useful for designing therapies to further enhance recovery from acute renal injury.
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PMID:Differential gene expression in the recovery from ischemic renal injury. 191 Jan 24

Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system.
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PMID:Splanchnic vasoconstriction and bacterial translocation after thermal injury. 192 2

Basic parameters of central and intracardiac hemodynamics were studied in 49 urological patients 24 of which with urolithiasis entered group I, 13 with hypertension-group II and 12 with varicocele-group III. The patients' age averaged 46.4, 41.6 and 28.6 years, respectively. The data were provided by routine clinical and laboratory examinations, ECG, one-passage radionuclide cardiography with 132I-albumin using a radiocirculographer of Hungarian manufacture and radiocardioanalyzer RKAZ-01 made in this country. Neither marked ischemic disturbances of the myocardium nor valvular defects were revealed. Ambiguous group-specific shifts presented in central and intracardiac hemodynamics. Total peripheral vascular resistance exhibited a moderate increase while left ventricular circulation time grew 1.5-2-fold. The greater resistance can be attributed to activation of renin-angiotensin system in prolonged ischemia of renal parenchyma due to nephrolithiasis. Group II patients demonstrated parallel elevation of arterial pressure, peripheral resistance, left ventricular performance and output suggesting myocardial functional stress. In group III there was a rise in blood volume, left ventricular performance and output, cardiac index, stroke volume. This myocardial overloading may result from changes in intravascular volumetric relations characteristic of hypervolemia. These hemodynamic changes reflect adaptation in urological patients and should be accounted for in treatment and operative interventions.
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PMID:[The radionuclide assessment of the central hemodynamic indices in patients with urolithiasis, arterial hypertension and varicocele]. 194 10

The dose-response effects of 6-h intravenous infusion of PGI2 (0, 5, 10, 25 or 75 ng/kg/min) or PGE1 (0, 25, 50, 100 or 300 ng/kg/min) on skin hemodynamics and viability were studied in 4 x 10 cm random pattern skin flaps (n = 24) raised on both flanks of the pig. Infusion of PGI2 or PGE1 was started immediately after intravenous injection of a loading dose 30 min before skin flap surgery. PGI2 infusion significantly (P less than 0.05) increased the total skin flap capillary blood flow at the dose of 10 ng/kg/min, compared with the control. However, the distance of blood flow along the skin flap from the pedicle to the distal end, i.e. perfusion distance, was not increased. Consequently, the length and area of skin flap viability was also not significantly increased. The effect of PGI2 infusion on skin blood flow was biphasic. Specifically, higher doses (greater than or equal to 25 ng/kg/min) of intravenous PGI2 infusion produced no beneficial effect on the skin flap capillary blood flow. PGI2 infusion at the dose of 10 or 75 ng/kg/min did not significantly increase plasma renin activities or plasma levels of norepinephrine compared with the control, therefore the biphasic effect of PGI2 on skin flap blood flow was not related to circulating levels of norepinephrine or angiotensin. Intravenous infusion of PGE1 did not produce any therapeutic effect on the skin capillary blood flow in the random pattern skin flaps at all doses tested. At the dose of 300 ng/kg/min, the mean arterial blood pressure was 17% lower (P less than 0.05) than the control, but the skin capillary flow still remained similar to the control. It was concluded that intravenous infusion of PGI2 or PGE1 was not effective in augmentation of distal perfusion or length of skin viability in the porcine random pattern skin flaps. Drug treatment modalities for prevention or treatment of skin flap ischemia is discussed.
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PMID:Efficacy of intravenous infusion of prostacyclin (PGI2) or prostaglandin E1 (PGE1) in augmentation of skin flap blood flow and viability in the pig. 205 39

The effects of oral zofenopril pretreatment were investigated in a chronic closed-chest pig model of ischemia and reperfusion. Pigs (25-35 kg) were pretreated orally with zofenopril (15 mg/day) on the 2 days prior to ischemia, which was evoked by the inflation of a catheter balloon in the left anterior descending coronary artery over 45 minutes. The catheter was then removed and the myocardium was reperfused. After 2 weeks, infarct properties were assessed by signal averaging of the body surface electrocardiogram and the inducibility of malignant ventricular tachyarrhythmias was tested with a programmed electrical stimulation protocol. A significant increase in the pressure-rate product (43 +/- 11%, mean +/- SEM), indicating the oxygen demand of the heart, was prevented by zofenopril (19 +/- 8%, p less than 0.05). Zofenopril reduced the peak efflux of adrenaline (1302 +/- 213 vs. 3201 +/- 760 pg/ml; p less than 0.05), noradrenaline (402 +/- 54 vs. 902 +/- 282 pg/ml; p less than 0.05), and of the adenosine catabolites inosine and hypoxanthine (56 +/- 4 vs. 78 +/- 9, pg/ml; p less than 0.05) in the coronary venous effluent. The efflux of the cytoplasmatic enzyme creatine phosphokinase was not significantly reduced after zofenopril (p = 0.08). No difference in plasma renin levels between the groups were found. After 2 weeks, late potentials were found only in the surviving animals from the untreated group, i.e., the voltage vector magnitude was more reduced, and a prolongation of the QRS duration and of the terminal low-amplitude part of the high-frequency QRS were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig. 207 80

Prolonged treatment with cyclosporine (CS) results in an irreversible renal lesion consisting of interstitial fibrosis and tubular atrophy, as well as prominent hyperplasia of the juxtaglomerular apparatus (JGA). Ischemia to the tubulointerstitial compartment caused by intense CS-mediated renal vasoconstriction may contribute significantly to the development of this lesion. To explore the potential role of volume contraction and activation of the renin-angiotensin system (RAS) in the genesis of this lesion, we have employed a recently described rodent model of chronic cyclosporine nephropathy (CCN). Over 28 days of CS therapy, animals received plain drinking water, 1% saline, or enalapril (ENAL), 50 mg/l in drinking water. At the end of 28 days, Na+ balance in saline-treated animals was markedly positive, and plasma volume was increased; however, glomerular filtration rate (GFR) did not change, and the tubulointerstitial lesion and JGA hyperplasia as evaluated by morphometric techniques were unaffected. Enalapril-treated animals were relatively hypotensive with lower GFR than CS controls. Enalapril conferred no protection against the development of tubulointerstitial disease and exacerbated the development of JGA hyperplasia and hyperkalemia. We conclude that volume contraction is not an important contributor to the reduced GFR, tubulointerstitial lesion, or JGA hyperplasia associated with long-term CS treatment. Blockade of the RAS also conferred no protection against the development of tubulointerstitial disease but resulted in worsening of JGA hyperplasia and hyperkalemia.
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PMID:Effects of chronic volume expansion and enalapril on chronic cyclosporine nephropathy. 218 76

The effects of angiotensin converting enzyme inhibitors (ACEIs), CGS 14831 (CAS 86541-78-8) and captopril, on the mechanical function and energy metabolism were studied in isolated rat hearts using global ischemia-reperfusion model. The myocardial tissue levels of ATP, creatine phosphate (CP) and pH were determined with 31P-nuclear magnetic resonance (31P-NMR). Global ischemia was induced by cross-clamping of the inflow line for 40 min. While thiol containing ACEI, captopril, significantly inhibited the ATP depletion and pH fall produced by ischemia, non-thiol compound, CGS 14831, did not have any influence on the ATP degradation and pH fall during ischemia. Both CGS 14831 (20 micrograms/ml) and captopril (80 micrograms/ml) have little influence on the mechanical function during the ischemia-reperfusion period. L-Cysteine (44.6 micrograms/ml) inhibited the pH fall significantly during the ischemia without exerting influence on the ATP degradation. These data suggest that local renin-angiotensin-aldosterone system does not play an important role in maintenance of the myocardial mechanical function during ischemia-reperfusion. The thiol residue of captopril is not responsible for the inhibitory effect of this compound on ischemia-induced ATP degradation. Some specific effect of captopril may play a role in the protective effect.
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PMID:Effects of two angiotensin converting enzyme inhibitors on the mechanical function and energy metabolism of isolated rat hearts. A nuclear magnetic resonance study with an active form of benazeprilat and captopril. 229 44

Components of the renin-angiotensin system (RAS) have been found in heart tissue and it is likely that angiotensin II (ANG II) is generated locally in the heart as in other organs. Pharmacological interference with converting enzyme (CE) inhibitors reduced CE activity and ANG II generation in the heart. To investigate whether local inhibition of CE in the heart with the CE inhibitor ramipril might contribute to the therapeutic effects, experiments were performed in isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, both single oral pretreatment with ramipril (1 mg/kg) or perfusion with the active moiety, ramiprilat (10 micrograms/ml), protected against ventricular fibrillation, which invariably occurred in control hearts during reperfusion. Reperfusion arrhythmias were aggravated by perfusion with ANG I and ANG II, but prevented by bradykinin. ANG I-enhanced ventricular fibrillations were completely eliminated during local CE inhibition with ramipril. The CE inhibitor also improved cardiodynamics. Coronary flow, left ventricular pressure, dp/dtmax, and myocardial oxygen consumption were increased in comparison to controls without changes in heart rate. In the perfusate of treated hearts, lactate dehydrogenase, and creatine kinase activities and lactate production, were reduced. Myocardial tissue levels of glycogen, ATP, and creatine phosphate were increased in ramipril-pretreated hearts whereas lactate was decreased. The results of these experiments in rat hearts suggest that local inhibition of CE by ramipril exerts protective effects after ischemia and reperfusion by reducing arrhythmias and improving cardiac function and metabolism, thus probably contributing to the therapeutic effects of CE inhibitors in cardiovascular diseases.
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PMID:Beneficial effects of the converting enzyme inhibitor, ramipril, in ischemic rat hearts. 243 98


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