Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 micrograms/kg followed by 25 micrograms/kg/min, i.v.) or nifedipine (3 micrograms/kg followed by 1 microgram/kg/min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (approximately 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil, or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine. 258 Jan 37

Rest technetium 99m-sestamibi uptake may underestimate myocardial viability in asynergic territories. Because nitrate administration was reported to improve thallium 201 uptake in perfusion defects, this study aimed to test the influence of nitrates on 99mTc-sestamibi uptake and on the tracer capability to recognize viable tissue in asynergic segments. In 23 patients with prior infarction and left ventricular dysfunction, regional wall motion was assessed by echocardiography before and after revascularization (13 segments/patient). Group 1 included 97 normokinetic; group 2, 97 hypokinetic; and group 3, 105 akynetic or dyskinetic segments; group 3 was divided into group 3A (72 segments unchanged after revascularization) and group 3B (33 segments with functional recovery). 99mTc-sestamibi uptake was graded using a scoring scheme in the same 13 segments both at rest and, on a separate day, injecting the tracer during isosorbide dinitrate infusion (ISDN). At rest, the mean 99mTc-sestamibi uptake decreased significantly from group 1 through group 3. With ISDN, the mean 99mTc-sestamibi uptake increased in all groups compared with rest, but the increase was significant only in groups 2 and 3, and within the latter, only in group 3B. Thus, with ISDN group 3B was no longer different from group 2. Only 6% of group 3A segments showed an improved uptake with ISDN, versus 33% of group 3B (P < .00005). At rest only 14 of 33 segments of group 3B showed a normal or slightly reduced uptake, whereas these were 25 of 33 with ISDN (P < .02). In conclusion, the acute administration of ISDN increases the uptake of 99mTc-sestamibi mainly in those asynergic territories that show postrevascularization functional recovery. Therefore, ISDN 99mTc-sestamibi imaging might improve the tracer capability to detect viable hibernating myocardium.
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PMID:Nitrate versus rest myocardial scintigraphy with technetium 99m-sestamibi: relationship of tracer uptake to regional left ventricular function and its significance in the detection of viable hibernating myocardium. 754 55

Somatosensory, motor, and visual sensory blockade were investigated after retrobulbar injection of 3 mL 2% lidocaine, prilocaine, or mepivacaine plus hyaluronidase (15 U/mL) and naphazoline nitrate (1:20,000) in 90 cataract patients (n = 30 per group). Before injection as well as 20 and 90 minutes after injection, and then every 30 minutes, the quality of the retrobulbar blockade was evaluated in terms of the following factors until full recovery of function: (1) corneal sensitivity at the three extraincisional quadrants as determined with an esthesiometer; (2) horizontal and vertical motility, and elevation of the lid; (3) visual acuity on an arbitrary score scale ranging from 0 (no light perception) to 6 (visual acuity > 0.05); and (4) the time required for recovery from retrobulbar anesthesia. The data were analyzed by one- (anesthetic) and two-factor (anesthetic and time) analysis of variance. Full somatic recovery of corneal sensitivity occurred within 247 +/- 10.2 minutes after lidocaine, within 221 +/- 9.2 minutes after prilocaine, and within 280 +/- 8.5 minutes after mepivacaine (F = 10.1; P < .0001). Full motor recovery (all muscles) occurred within 290 +/- 5.8 minutes after lidocaine, within 258 +/- 5.7 minutes after prilocaine, and within 295 +/- 4.8 minutes after mepivacaine (F = 13.3, P < .0001). On the average, visual acuity decreased most after mepivacaine and least after lidocaine administration, although the differences between the three anesthetics in this regard were not significant. One patient temporarily lost vision after mepivacaine administration. Overall, the somatosensory and motor blockade were most pronounced after mepivacaine.
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PMID:Retrobulbar blockade of somatic, motor, and visual nerves by local anesthetics. 805 71

1. The pathophysiological significance of ATP-sensitive K+ (KATP) channels in the central nervous system is not fully understood. In this study the effects of nicorandil (a hybrid vasodilator having a dual mechanism of action as a K+ channel opener and a nitrate) on the recovery of the spinal cord reflex potentials after spinal cord ischaemia were examined and compared with those of pinacidil and nitroprusside in anaesthetized spinal cats. 2. Spinal cord ischaemia was produced by occlusion of the thoracic aorta and the bilateral internal mammary arteries for 10 min. Regional blood flow in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of the tibial nerve, were recorded from the lumbo-sacral ventral root. The recovery process of spinal reflex potentials was reproducible when the occlusion was repeated twice at an interval of 120 min. 3. Pretreatment with nicorandil (30-100 micrograms kg-1) accelerated the recovery of PSR potentials after spinal cord ischaemia. Such an accelerating effect on the recovery of PSR potentials was also shared by pinacidil (100 micrograms kg-1), another K+ channel opener. In addition, the accelerating effect of nicorandil (100 micrograms kg-1) on the recovery of PSR potentials was abolished by co-administration of glibenclamide (3 mg kg-1), a sulphonylurea KATP channel blocker. Nitroprusside (8 micrograms kg-1min-1) retarded rather than improved the recovery of PSR potentials after spinal cord ischaemia. All of these drugs failed to improve the spinal cord blood flow during ischaemia and reperfusion. 4 These results suggest that nicorandil promotes the recovery of polysynaptic reflex potentials after spinal cord ischaemia by opening the KATP channels of neurones rather than by increasing local bloodflow. K+ channel openers may exert a salutary effect on the functional recovery of the ischaemic spinal cord.
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PMID:Effects of nicorandil on the recovery of reflex potentials after spinal cord ischaemia in cats. 852 65

Detection of myocardial viability is an important clinical issue in the time course of acute myocardial infarction and in chronic coronary artery disease. The wide availability of myocardial revascularization procedures requires a refinement of specific indications for revascularization whenever left ventricular failure is the most prominent feature of coronary artery disease. In this instance the risk/benefit ratio has to be attentively evaluated with diagnostic tests able to predict favourable changes in regional and global left ventricular function, symptoms, life quality, risk of adverse events and ultimately prognosis. 201Tl has been shown to provide clinically televant information regarding the presence of myocardial viability in patients with extensive regional or global ventricular dysfunction. However, the increasing use of 99mTc labeled myocardial perfusion agents requires a careful evaluation of diagnostic and predictive accuracy of these agents also for the issue of myocardial viability. The widely accepted opinion of a lower predictive accuracy of these agents compared to 201Tl could be no longer true. The available clinical and experimental data indicate, at least for 99mTc-sestamibi, a comparable accuracy when independent and clinically relevant gold standard of viability like post-revascularization functional recovery is considered. Preliminary data indicate that protocols, like nitrate administration, slow infusion or delayed imaging, and accurate quantitation of 99mTc-sestamibi SPECT studies could enhance the predictive accuracy to a level comparable or even better than that of 201Tl and similar to the more demanding PET technology.
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PMID:Detection of myocardial viability with 99mTc-labelled myocardial perfusion agents. 868 Oct 15

Reintroduction of high levels of molecular oxygen after a hypoxic period is followed by a burst of nitric oxide (NO), peroxynitrite, and oxygen free radicals (OFR), which are highly cytotoxic. This study indicates that hyperoxic reoxygenation of cyanotic immature hearts on cardiopulmonary bypass (CPB) induces a reoxygenation injury and that, by reducing NO and OFR production during institution of CPB with subsequent reoxygenation under blood cardioplegic arrest, this oxygen-related damage can be avoided and biochemical and functional status improved. Of 25 immature piglets (3-5 kg, two to three weeks old), 6 underwent one hour of CPB including thirty minutes of aortic clamping with substrate-enriched modified blood cardioplegia (hypocalcemic, alkalotic, and hyperosmolar; warm induction-cold replenishment-warm reperfusion) without preceding hypoxia (controls). Nineteen others were made hypoxic (arterial [Po2] 20-30 mmHg) for up to two hours by lowering the fraction of inspired oxygen (FIO2) on ventilator. These hypoxic piglets were then reoxygenated on CPB at different Po2 levels (hyperoxic, normoxic, or hypoxic) for five minutes, followed by the aforementioned blood cardioplegic (BCP) arrest regimen. Myocardial conjugated diene (CD) production as a marker of lipid peroxidation, and NO production, determined as its spontaneous oxidation products, nitrite (NO2-) and nitrate (NO3-), were assessed during blood cardioplegic induction, and antioxidant reserve capacity was determined by incubating myocardium in the oxidant t-butylhydroperoxide (t-BHP). Myocardial function was evaluated from end-systolic elastance (Ees, conductance catheter). Blood cardioplegic arrest caused no functional or biochemical changes in normoxic control immature piglets. In contrast, brief reoxygenation at PO2 > 400 mmHg, followed by BCP-arrest (hyperoxic) resulted in marked CD production (42 +/- 4 vs 3 +/- 1 A233 nm/minute/100 g; P < 0.05), and NO production (4500 +/- 500 vs 450 +/- 32 mmol/minute/100 g; P < 0.05) during blood cardioplegic induction, reduced antioxidant reserve capacity (malondialdehyde [MDA] at 4.0 mM of t-BHP: 1342 +/- 59 vs 958 +/- 50 nM/g protein; P < 0.05), and caused profound myocardial dysfunction; Ees recovered only 21 +/- 2% (vs 104 +/- 7; P < 0.05), despite the blood cardioplegic regimen shown to be cardioprotective in control normoxic piglets. Conversely, controlling initial PO2 to normoxic (100 mmHg) or hypoxic (20-30 mmHg) levels reduced lipid peroxidation (CD production 16 +/- 2, 2 +/- 1 A233nm/minute/100 g) and NO production (1264 +/- 736, 270 +/- 182 mmol/minute/100 g), restored antioxidant reserve capacity (MDA at 4.0 mM of t-BHP: 940 +/- 95, 982 +/- 88 nM/g protein), and allowed significant functional recovery (58 +/- 11% and 83 +/- 8%), in a PO2-dependent fashion. The authors conclude that reoxygenation of hypoxemic immature hearts by initiating hyperoxic CPB causes oxidant-related damage characterized by lipid peroxidation, enhanced NO production, and reduced antioxidants, leading to functional depression that nullifies the cardioprotective effects of blood cardioplegia. These detrimental effects can be reduced in a PO2-dependent fashion by controlling initial PO2 on CPB and subsequent reoxygenation during blood cardioplegic arrest.
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PMID:Nitric-oxide-induced reoxygenation injury in the cyanotic immature heart is prevented by controlling oxygen content during initial reoxygenation. 907 Nov 94

The ATP-sensitive potassium channel (KATP channel) has been implicated in the mechanism underlying ischaemic preconditioning protection. This study based on human atrium compared the protective effects of ischaemic preconditioning with pre-operative nicorandil (a KATP channel opener with nitrate actions). We also examined the added effect of ischaemic preconditioning to that of nicorandil on ischaemic protection. The protective effects of other KATP channel openers devoid of nitrate actions were also examined. Atrial trabeculae harvested from patients undergoing routine myocardial revascularisation were divided on the basis of whether patients had been ingesting nicorandil orally preoperatively. Trabeculae were superfused with oxygenated Tyrode's solution and following stabilisation underwent 90 minutes simulated ischaemia followed by 120 minutes reoxygenation (n = 6 per group). Atrial trabeculae exposed to nicorandil underwent either no treatment (N), or ischaemic preconditioning (N + PC) using 3 minutes simulated ischaemia and 7 minutes reoxygenation prior to the 90 minutes simulated ischaemia. Similarly trabeculae not exposed to nicorandil underwent either no treatment, controls (C), or ischaemic preconditioning (PC). The experimental endpoint was recovery of contractile function presented as percentage baseline function. Further groups were examined using other KATP channels openers with and without ischaemic preconditioning. In the control group, following 120 minutes reoxygentation the recovery of function reached 28.8 +/- 3.5%. In contrast, exposure to nicorandil alone improved recovery of function (55.5% +/- 5.3) to a similar extent as PC (55.3% +/- 2.5) when compared to controls (p < 0.05, ANOVA). The addition of ischaemic preconditioning to nicorandil exposure abolished protection (29.7% +/- 3.1 ). Findings were confirmed using the other KATP channels openers. Clinically available nicorandil appears to afford ischaemic protection to isolated human atrial muscle. The addition of a short ischaemic episode to nicorandil exposure seems to completely abolish this protection. Although the mechanism underlying this effect remains unknown, we believe that this observation may have clinical implications.
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PMID:Ischaemic preconditioning may abolish the protection afforded by ATP-sensitive potassium channel openers in isolated human atrial muscle. 934 32

We previously showed that preoperative nicorandil, a hybrid potassium channel opener and nitrate compound, conferred cardioprotective effects in a hypoxia/reoxygenation model of isolated human atrial muscle by using functional recovery as an end point, and that ischaemic preconditioning surprisingly abolished the protection afforded by nicorandil. In view of this paradoxic result, this study was undertaken to assess whether ischaemic preconditioning influences any protective effect of nicorandil by using infarct size as an end point. In addition, we investigated the underlying mechanisms of the protective action of nicorandil. Rabbits underwent a midline sternotomy under anaesthesia. A left coronary branch was occluded for 30 min followed by 120 min of reperfusion. Nicorandil (100 microg/kg bolus + 10 microg/kg/min) was given intravenously 30 min before coronary occlusion and continued to the time of reperfusion (early treatment) or 5 min before reperfusion and continued throughout reperfusion (late treatment). Ischaemic preconditioning was achieved by a single episode of 5-min coronary occlusion followed by 10-min reperfusion before the 30-minute occlusion in the presence or absence of nicorandil. Risk volume and infarct volume were determined by fluorescent microspheres and tetrazolium staining, respectively. Early treatment with nicorandil conferred a significant decrease in percentage of infarct size within the risk zone (24.9 +/- 2.9%) when compared with control (39.2 +/- 4.3%; p < 0.01). Late treatment with nicorandil had no effect on infarct size (43.5 +/- 3.4%). Ischaemic preconditioning also resulted in significant reduction in infarct size (13.4 +/- 4.3%; p < 0.01 vs. control). The combination of ischaemic preconditioning with nicorandil (early treatment) showed an intermediate protective efficacy between early treatment with nicorandil alone and ischaemic preconditioning alone (18.1 +/- 4.2%; p < 0.01 vs. control). Nitroglycerin (10 microg/kg bolus + 1 microg/kg/kg/min, i.v.) given before and during ischaemia tended to reduce infarct size, but the effect was not statistically significant (28.9 +/- 2.9%; p > 0.05 vs. control). Although an adenosine triphosphate (ATP)-sensitive potassium channel blocker, 5-hydroxydecanoate (5 mg/kg, i.v.) by itself had no effect on infarct size (38.8 +/- 3.6%), the protective effect of nicorandil was abolished by 5-hydroxydecanoate (37.7 +/- 5.8%; p < 0.05 vs. early treatment of nicorandil). There were no differences in area at risk or haemodynamics between groups. Our results show that nicorandil has a protective effect against myocardial infarction in our rabbit model when infused before and during ischaemia, but not during reperfusion, and the protective effect is abolished by an ATP-sensitive potassium channel blocker. Furthermore, the addition of ischaemic preconditioning does not detrimentally influence the effect of nicorandil. This suggests that nicorandil can confer an infarct-limiting effect by opening of ATP-sensitive potassium channels with or without intermittent ischaemia, as may happen in patients with unstable angina.
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PMID:Myocardial protection afforded by nicorandil and ischaemic preconditioning in a rabbit infarct model in vivo. 945 80

To evaluate whether nitroglycerin administered before the injection of sestamibi improves the detection of viable but hypoperfused myocardium, 41 post-infarction patients with left ventricular dysfunction underwent echocardiography and SPET at rest and after nitrate administration. In 25 revascularized patients, perfusion at rest and contractility were assessed 3-4 months after coronary artery bypass grafting. Perfusion (PI) and wall motion indices (WMI) were calculated for each revascularized area. There was a strong correlation between contractility and perfusion defect (r = 0.58, P < 0.0001). Nitrates significantly reduced the number of perfusion defects in hypokinetic (delta PI = 0.25 +/- 0.66) and akinetic (delta PI = 0.32 +/- 0.62), but not in dyskinetic (delta PI = 0.08 +/- 0.62), segments. Twenty-five revascularized patients had 110 asynergic segments and 136 segments with a resting perfusion defect. Function improved in 42% and perfusion in 64% of segments after surgery. Viable segments had a lower PI at rest (2.78 +/- 1.38 vs 3.86 +/- 1.29, P < 0.001) and a lower WMI (2.46 +/- 0.50 vs 2.79 +/- 0.59, P = 0.002). Nitrates reduced the number of perfusion defects slightly more in viable than non-viable segments (delta PI = 0.58 +/- 0.89 vs 0.30 +/- 0.46, P = 0.06). Contractility and perfusion at rest were the most important predictors of functional recovery. The sensitivity and specificity in predicting contractile improvement were 74% and 64% for resting SPET respectively, and 80% and 50% for nitrate SPET respectively. Nitrate administration significantly reduces perfusion defects in asynergic regions; however, its usefulness in predicting contractile recovery may be limited owing to its low specificity. Contractility and sestamibi uptake at rest were the strongest predictors of post-operative wall motion improvement.
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PMID:99Tcm-sestamibi tomoscintigraphy at rest and after nitrate administration in predicting wall motion recovery after revascularization. 988 4

Pentaerithrityltetranitrate (PETN) is an organic nitrate ester with high selectivity to venous vessels and little development of tolerance. Here we report experimental results concerning the hemodynamic and antiischemic effects of intravenously administered PETN. The experiments were performed with anesthetized, open-chest minipigs (25 to 35 kg body weight [bw]). PETN (0.125, 0.25, 0.5 mg/kg bw, i.v.) dose-dependently decreased left ventricular systolic pressure without change in peripheral vascular resistance. A reflex increase in heart rate returned to normal within 20 minutes (0.125 and 0.25 mg/kg). PETN (0.5 mg/kg) also transiently (10 minutes) decreased left ventricular contractility. In additional experiments, myocardial infarction was induced by LAD occlusion (1 hour), followed by reperfusion (3 hours). PETN (0.6 mg/h, i.v.) was administered starting 20 minutes before ischemia until the end of reperfusion. While PETN did not cause hemodynamic changes, infarct size was significantly decreased compared with vehicle (56 +/- 6% vs 83 +/- 3% of area at risk, p < 0.05). Regional contractile function (ultrasound crystals) was completely abolished during ischemia and did not recover during 3 hours reperfusion in control hearts. However, PETN-treated pigs showed partial functional recovery (19 +/- 5%, p < 0.05 vs vehicle) during the first hour of reperfusion. Histologic evaluation revealed a decreased number of granulocytes accumulated in the ischemic myocardium of PETN-treated animals. Accordingly, in-vitro experiments showed a reduction by PETN of the adherence of HL-60 cells differentiated to granulocytes to vascular smooth muscle cells. Therefore, PETN reduced infarct size and improved myocardial function after LAD occlusion and reperfusion. It is concluded that the intravenous administration of PETN might be of advantage in the treatment of acute myocardial ischemia.
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PMID:[Experimental study of the effect of pentaerythritol tetranitrate in acute myocardial infarct]. 1114 79


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