Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Na(+)-HCO3- coinflux carrier and the Na(+)-H+ antiport have both been shown to contribute to recovery from intracellular acidosis in cardiac tissue. We have investigated the participation of these mechanisms as well as metabolite (lactate and CO2) washout in the recovery of pHi after myocardial ischemia. Isovolumic ferret hearts were Langendorff-perfused with either HCO3(-)-buffered or nominally HCO3(-)-free (HEPES-buffered) medium at 30 degrees C. pHi was estimated from the chemical shift of the 31P-nuclear magnetic resonance signal of intracellular PO4-, and net H+ efflux rates were calculated at pHi 6.80. The H+ efflux rate during reperfusion, after 10 minutes of global ischemia, was 15.5 +/- 1.9 mmol.l-1 x min-1 (n = 10) in hearts perfused with HCO3(-)-buffered medium and 8.2 +/- 1.5 mmol.l-1 x min-1 (n = 9, p < 0.01) in hearts perfused with HEPES-buffered medium. HCO3- influx, assessed either by inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (20 microM) or by initially perfusing hearts with HEPES-buffered medium but reperfusing with HCO3(-)-buffered medium, accounted for 3.5-4.9 mmol.l-1 x min-1, and CO2 efflux accounted for 3.8-6.2 mmol.l-1 x min-1 of the additional H+ efflux in HCO3(-)-buffered medium. H(+)-coupled lactate efflux, measured by NAD(+)-linked spectrophotometric assay and inhibited by the sarcolemmal monocarboxylate transport inhibitor 4,4'-dibenzamidostilbene-2,2'-disulfonate (0.25 mM), contributed 3.7-6.2 mmol.l-1 x min-1. H+ efflux via the 5-(N-ethyl-N-isopropyl)amiloride-sensitive Na(+)-H+ antiport was 1.0-2.9 mmol.l-1 x min-1. pHi recovery after ischemia is therefore principally mediated by metabolite (lactate and CO2) washout. Na(+)-coupled acid extrusion contributed approximately 35% of total H+ efflux in this system. However, the associated Na+ entry (approximately 5 mmol.l-1 x min-1) may contribute to Ca2+ overload after reperfusion.
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PMID:Mechanisms of pHi recovery after global ischemia in the perfused heart. 838 98

Myocardial ischemia is associated with an intracellular acidosis recovering after reperfusion. Alpha 1-adrenergic stimulation (alpha 1) exacerbates ischemic injury and triggers ventricular arrhythmias during the reperfusion phase. We have tested the hypothesis that the arrhythmogenic effect of alpha 1 is due to a cytosolic alkalinization secondary to proteinkinase C (PKC)-dependent activation of the sarcolemmal Na+/H+ exchanger. In addition, the effect of the 2 distinct receptor subtypes, alpha 1A and alpha 1B, has also been evaluated. We used single, enzymatically dissociated, adult rat ventricular myocytes. Cells were loaded with the ester derivative of the Ca2+ probe, indo-1 or with the intracellular pH probe SNARF-1. Fluorescence was monitored simultaneously with contractility and was taken as an index of intracellular [Ca2+] or as pHi value. Cells on a stage of an inverted microscope were superfused with a bicarbonate buffer continuously gassed with 95% O2 and 5% CO2 (pH = 7.37; Ca2+ 1.5 mM) and electrically stimulated at 0.5 Hz, at 25 degrees C. Alpha 1 (phenylephrine 50 microM + nadolol 1 microM) increased twitch amplitude and pHi (delta pHi = 0.05 +/- 0.01; pHi in control = 7.24 +/- 0.06, n = 10; p < 0.05). This effect was abolished by the PKC inhibitor staurosporine (5 nM), by overnight (12-24 hours) exposure to 0.2 microM phorbol esters and by the perfusion with 10 microM ethylisopropylamiloride (EIPA), a Na+/H+ exchange inhibitor. During 15 min of hypercarbic acidosis, achieved by switching to a buffer equilibrated with 85% O2 and 15% CO2 (pH = 7.01), alpha 1 had a more pronounced effect on pHi (delta pHi = 0.11 +/- 0.02; pHi in control = 7.02 +/- 0.04, n = 10; p < 0.05). During the 10 min following the removal of acidosis, alpha 1 induced aftercontractions in 75% (n = 20) versus only 25% (n = 8) of the cells in the absence of phenylephrine (p < 0.05). Superfusion with 10 microM EIPA (n = 6) abolished the occurrence of aftercontractions. Selective alpha 1A-adrenergic receptors stimulation (alpha 1 + 2 microM CEC, which inactivates alpha 1B receptors) further increased them (92%, n = 12) whereas selective alpha 1B-adrenergic receptors stimulation (alpha 1 + 2 microM WB-4101, a alpha 1A receptors antagonist) greatly reduced the occurrence of aftercontractions (11%, n = 18). These results show that the PKC-mediated activation of the Na+/H+ exchanger is the mechanism for the arrhythmias induced by alpha 1 during simulated reperfusion after a period of acidosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Stimulation of the alpha-1 adrenergic receptors during simulated reperfusion after myocardial acidosis. The evidence for an arrhythmogenic role of the Na+/H+ exchanger]. 838 75

Effective pulmonary capillary pressure and extravascular lung water were investigated in dogs (n = 9) with normal heart function and after development of acute myocardial ischaemia. During control, no impairment of cardiopulmonary performance was observed. Extravascular lung water was in the normal range (8.1 +/- 2.8 ml.kg-1) and the effective pulmonary capillary pressure accounted for 1.36 +/- 0.53 kPa (10.2 +/- 4 mmHg). No correlation between extravascular lung water and effective pulmonary capillary pressure was observed (r2 = 0.347, P = 0.06). Arterial (RPA) and venous pulmonary resistance (RPV) were 70 +/- 15% and 30 +/- 6%, respectively. Acute myocardial ischaemia was induced by one stage occlusion of the left anterior descending (LAD) coronary artery; measurements during the ischaemia phase were performed 60 min following LAD occlusion. Myocardial ischaemia resulted in moderate changes of cardiac output, heart rate and left ventricular end-diastolic pressure. Oxygenation deteriorated, but no hypoxaemia occurred in any animal and CO2 elimination remained unchanged. Extravascular lung water was elevated (16.5 +/- 7.9 ml.kg-1, P < or = 0.01), and effective pulmonary capillary pressure was higher when compared with the control state (2.32 +/- 1.05 kPa (17.4 +/- 7.9 mmHg), P < or = 0.01). There was a significant correlation between both parameters (r2 = 0.528, P < or = 0.05). Longitudinal distribution of pulmonary vascular resistance was altered, and RPA decreased to 60 +/- 13% (P < or = 0.05), while RPV increased to 40 +/- 8% (P < or = 0.05). It is concluded that development of lung oedema is related to elevated effective pulmonary capillary pressure in dogs with acute myocardial ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effective pulmonary capillary pressure in experimental myocardial ischaemia. 850 65

Recently, much attention has been paid to promote endovascular intervention for the patients with ischemic heart disease and occlusive peripheral arterial disease. There are a few patients for whom coronary artery bypass grafting and repeated PTCA can not be carried out, because small branches or diffuse stenoses of the coronary arteries. To resolve these problems author tried to supply arterial blood from the left ventricle into the ischemic myocardium through new channels created into the myocardium by CO2 laser. Consequently, it could be clarified that this procedure could be hemodynamically, or histologically used as an alternative transmyocardial revascularization (TMR) by laser. Finally, this TMR was clinically employed in 1985. Mechanism, technique and its results of TMR are discussed in detail.
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PMID:[Current status and 21 century in the laser transmyocardial revascularization (LTMR)]. 864 35

The use of carbon dioxide to create a cavity for the operation of laparoscopic cholecystectomy leads to serious complications of the cardiovascular system; consequently, patients with ischaemic heart disease can be put at greater risk. For example, on reaching an intra-abdominal pressure of 15mmHg, a fall of about 35% of the static compliance was observed. Upon using the Laparolift, these influences on the respiratory system were not detected, and the rise in systemic vascular resistance usually seen with the CO2-pneumoperitoneum did not occur. From the anaesthetist's viewpoint the Laparolift was helpful in the treatment of patients with serious limitations of cardiac function.
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PMID:The abdominal lift: is there any advantage for the critically ill patient? 884 27

The recirculation fraction (RF) of the activator Ca2+ of the cardiac muscle is an index of the fraction of the internally released Ca2+ sequestered by the sarcoplasmic reticulum during each contraction-relaxation cycle. Estimates of the RF were obtained by the slope method during the decline of the post-rest potentiation in the isolated aorta-perfused rat heart. Normalized contractile force P(max) of the second post-interval beat, B2, was plotted as a function of the first post-interval beat, B1, and fitted by a linear regression line. The correlation coefficient (r2) and the slope of the line were computed. Under the control experimental perfusion with oxygenated (95% O2-5% CO2) Krebs-Henseleit buffer ([Ca2+]0 1.25 mM, 34 degrees C, ph 7.40), the slope of the line, representing the RF of the rat left ventricle, was 0.73 +/- 0.01 (mean +/- SE) (r2 0.95 +/- 0.01). Increasing the stimulation frequency from 1 to 3.3 Hz produced a negative inotropic effect and significantly reduced the RF, to 0.17 +/- 0.02. Positive inotropic interventions significantly increased the RF, to 0.95 +/- 0.05 with [Ca2+]0 4 mM and to 0.92 +/- 0.04 with a 30% reduction in [Na+]0, whereas inhibition of Ca2+ release from the sarcoplasmic reticulum by ryanodine (1 microM) perfusion significantly reduced the RF, to 0.68 +/- 0.05 from the control ([Ca2+]0 2.5 microM) value of 0.81 +/- 0.05. These findings indicate that RF is a good index of the inotropic status of the rat heart. The time course of changes in RF after graded ischemia-reperfusion indicated a significant increase in the reperfusion RF between 30 and 60 min of ischemia accompanied by a significant rise in left ventricular end-diastolic pressure (LVEDP) and a significant fall in P(max), indicating an irreversible phase of the injury. During the reversible phase ( < 30 min) of the ischemia-reperfusion injury, no significant changes in RF were detected. It was concluded that RF, as derived from the simple interval-force relationship, is a good predictor of the reversible and irreversible phases of the myocardial ischemia-reperfusion injury and index of the extent of Ca2+ loading of the sarcoplasmic reticulum.
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PMID:Recirculation fraction of the activator Ca2+: index of the extent of Ca2+ loading of rat myocardium during ischemia-reperfusion. 896 47

Spreading of laparoscopic techniques caused changes in anaesthesiological contraindications. In the first period laparoscopy was contraindicated in ischemic heart disease (IHD). Early mobilisation and short postoperative period are positive goals, IHD was taken out of contraindications. Present study compares changes in circulatory, blood gas and acid-base balance values during laparoscopic cholecystectomy (LC) in groups of patients ASA I-II. and ASA III. with IHD. There were 30 patients in group ASA I-II, 30 patients with IHD in category of ASA III. investigated during LC. Fifteen patients of both groups went under Propofol-Fentanyl (TIVA) anaesthesia, others were on Propofol-Fentanyl-N2O (IVA) protocol. All of them got also Atracurium. Pulse rate, mean arterial pressure, O2 saturation and end tidal CO2, blood gases and acid-base state were recorded before induction, after CO2 insufflation, after desufflation, 1 and 3 hours postoperatively. After CO2 insufflation there was a moderate tachycardia in both ASA III. groups (74/min-->88/min). In all groups pCO2 increased (40-->48 mmHg) but normalised till the 3rd postoperative hours (42 mmHg). Ventricular extrasystoles appeared in 3 ASA III. patients in IVA group. Three high risk patients had serious metabolic acidosis postoperatively. Present time the ischaemic heart disease does not contraindicates laparoscopic interventions. TIVA with Propofol is better choice because of its favourable effects on circulation and acid-base balance. Using N2O caused higher grade of intestinal distension. The cardio-respiratory, blood gas parameters and acid-base balance have to be monitorised in perioperative period of laparoscopic surgery.
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PMID:Anaesthesiological indications and contraindications of minimally invasive surgery. 940 93

Studies exploring methods to revascularize the ischemic myocardium through increasing the collateral circulation were conducted by many investigators before the advent of myocardial revascularization by aortocoronary bypass grafting. Present alternatives, including surgical intervention, balloon angioplasty, thrombolytic therapy, and medical management, are the treatment of choice for the majority of patients. There are, however, a number of patients who do not respond to conventional management strategies. A clinical protocol was designed to assess the efficacy of transmural revascularization by creating CO2 laser channels in the ischemic areas of the left ventricle. Channels were made from the epicardial surface of the heart, through the ventricle, to the endocardium. Patients entered in the study were candidates for bypass grafting, but because of the pathology of the coronary artery system, bypass grafting alone would have resulted in incomplete revascularization. Postoperative thallium stress tests and left ventriculography indicate that channels have remained patent and that they perfuse the myocardium. Myocardial revascularization by laser channels may offer a viable adjunct in the treatment of ischemic heart disease.
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PMID:Clinical and histological evaluation of laser myocardial revascularization. 1014 64

Myocardial ischemia/reperfusion is well recognized as a major cause of apoptotic or necrotic cell death. Neonatal rat cardiac myocytes are intrinsically resistant to hypoxia-induced apoptosis, suggesting a protective role of energy-generating substrates. In the present report, a model of sustained hypoxia of primary cultures of Percoll-enriched neonatal rat cardiac myocytes was used to study specifically the modulatory role of extracellular glucose and other intermediary substrates of energy metabolism (pyruvate, lactate, propionate) as well as glycolytic inhibitors (2-deoxyglucose and iodoacetate) on the induction and maintenance of apoptosis. In the absence of glucose and other substrates, hypoxia (5% CO2 and 95% N2) caused apoptosis in 14% of cardiac myocytes at 3 h and in 22% of cells at 6-8 h of hypoxia, as revealed by sarcolemmal membrane blebbing, nuclear fragmentation, and chromatin condensation (Hoechst staining), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and DNA laddering. This was accompanied by translocation of cytochrome c from the mitochondria to the cytosol and cleavage of the death substrate poly(ADP-ribose) polymerase. Cleavage of poly(ADP-ribose) polymerase and DNA laddering were prevented by preincubation with the caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk) and benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone (zDEVD-fmk), indicating activation of caspases in the apoptotic process. The caspase inhibitor zDEVD-fmk also partially inhibited cytochrome c translocation. The presence of as little as 1 mM glucose, but not pyruvate, lactate, or propionate, before hypoxia prevented apoptosis. Inhibiting glycolysis by 2-deoxyglucose or iodoacetate, in the presence of glucose, reversed the protective effect of glucose. This study demonstrates that glycolysis of extracellular glucose, and not other metabolic pathways, protects cardiac myocytes from hypoxic injury and subsequent apoptosis.
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PMID:Glucose uptake and glycolysis reduce hypoxia-induced apoptosis in cultured neonatal rat cardiac myocytes. 1021 35

To explore the role of adrenomedullin (ADM) in pathophysiology of ischemic heart disease, we investigated the effects of hypoxia on the production and secretion of ADM in cultured human coronary artery endothelial cells. Treatment with hypoxia (5% CO2/94% N2/1% O2) for 6 and 12 h increased expression levels of ADM mRNA 2.2-fold and fivefold compared with the normoxia control, respectively. The levels of immunoreactive ADM in the media were increased by 12-h hypoxia about fivefold compared with the control (39.0+/-1.1 fmol/10(5) cells per 12 h under hypoxia and 7.9+/-0.4 fmol/10(5) cells per 12 h under normoxia; P<0.01, n = 4, mean +/- SEM). Reverse-phase high-performance liquid chromatography of the extracts of culture media under normoxia and hypoxia showed one major peak eluting in the position of human ADM standard. The production and secretion of ADM were increased in cultured human coronary artery endothelial cells under hypoxia. ADM may therefore play an important pathophysiological role in ischemic heart disease.
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PMID:Induction of adrenomedullin by hypoxia in cultured human coronary artery endothelial cells. 1047 34


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