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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.
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PMID:Contribution of tissue acidosis to ischemic injury in the perfused rat heart. 0 93

The rate of coronary flow reaching the oxygen-linited heart appears to be crucial in determining the myocardial tissue metabolic response. The tissue metabolic response to anoxia, well studied in hearts perfused with anoxic media, differs in many important ways from the response to ischemia. In regional ischemia (developing infarction) there is still a residual oxygen uptake which is reduced approximately to the same extent as the delivery of O2; there is also decreased delivery of substrates and decreased removal of CO2, H+, and lactate, with increased concentrations of these metabolites. Contents of hexose monophosphates rise rather than fall in anoxia. Measurements of glycolytic intermediates show an initial burst of accelerated glycolytic flux lasting less than 1 minute after coronary artery ligation; thereafter rates of flux decrease to control values or even less at 120 minutes. Relative inhibition of phosphofructokinase (PFK) activity may be explained by a slow rate of fall of ATP and a developing intracellular acidosis. In this model, glucose accounts for a greater part of the residual oxidative metabolism than does free fatty acid (FFA).
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PMID:Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia. 0 2

The purpose of this study was to examine the magnitude of the influence of coronary arterial pH (pHa) on myocardial oxygen uptake (MV 02). In order to isolate and control the recognized determinants of MV02, a perfused heart preparation was developed which permitted control of heart rate and pressure and flow work. A perfusion system was used which allowed independent regulation of O2 N2 and CO2 flow to a membrane lung and precise control of coronary blood flow. Myocardial oxygen delivery (Ca02 x flow) could be held constant (+/- 1%) during 4 hours of perfusion. Catheter decompression of both ventricles prevented any external pressure or flow work. Blood temperature was maintained at 37.27 +/- 0.07degrees C. Perfusing blood pH was related initially to spontaneous heart rate in five dogs: pulse = 82 pH - 487. In 12 subsequent animals heart rate was fixed. MV02 was directly and significantly related to coronary arterial pH in all animals studied: MVO2% = 109 pH - 143 (r = 0.823). An increase in pHa of 0.1 will increase MV02 by 10.9%. This study isolates pH as a determinant of myocardial oxygen uptake and indicates that progressive alkalosis induces increased myocardial oxygen uptake. This must be recognized in the treatment of patients with compromised myocardial function and rerional areas of ischemia.
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PMID:The influence of coronary arterial pH on myocardial oxygen demand. 1 52

The author studies only the usual investigations required for watching E.C.C. during the operatory period and directly afterwards. During E.C.C., one must essentially oversee the flow (2,4l/m2 or 70 ml/kg), the arterial pressure (70 torrs) essential factor for myocardiac injection, the C.V.P., where excess is factor of cerebral oedema, the peripheric vascular resistances (P.V.R.) which inform on the level of vasomotoricity. Control of pulmonary capillary pressure (P.C.P.), which is under E.C.C. the reflection of the left ventricular pressure (L.V.P.) is also a capital element of this watching (any elevation of L.V.P. is factor of sub-endocardiac ischemia and of acute pulmonary edema). In post E.C.C., the same parameters will be watched. A cardiac output equal or inferior to 2 l/m2 involve an immediate treatment. The C.V.P. allows adaptation of blood quantity. Calcul of V.P.R. sets treatment of low cardiac output. C.P.C. control allows evaluation of left ventricular efficacity. These datas must be completed by calcul of subendocardiac viability by studying the arterial pressure curves which inform on oxygen supply and demand, and by the contractility index measure (aortic output speed and measure of systolic interval).
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PMID:[Hemodynamic parameters which should be watched during and immediately after extracorporeal circulation]. 1 25

This study tests the hypothesis that postischemic myocardial depression can be reduced by providing an initial reperfusate pH which is appropriate for myocardial temperature (i.e., metabolic systems function optimally when pH is kept slightly alkaline to the neutral point, which changes with temperature in concordance with the pK of water). Ten dogs underwent 1 hour of ischemic arrest with topical hypothermia (intramyocardial temperature 16+/-2 degrees C). The initial reperfusate (500 cc of blood from the extracorporeal circuit) was infused (100 cc/minute) into the proximal aorta just before removing the cross-clamp. Reperfusate pH was kept at 7.4 in five dogs (control) and raised to 7.8 with THAM [tris (hydroxymethyl) aminomethane] in five dogs. Measurements 30 minutes after reperfusion showed that raising reperfusate pH to 7.8 resulted in (1) higher subendocardial blood flows (109+/-20 vs 61 cc+/-8 cc/100 gm/minute), (2) redistribution of postischemic blood flow toward the subendocardium (endocardial/epicardial flow 1.25+/-0.1 vs 1.0+/-0.03), (3) higher left ventricular oxygen uptakes (0.046 vs 0.033 cc/100 gm/beat), (4) better postischemic left ventricular compliance (56+/-3% more compliant), and (5) improved left ventricular performance (88+/-7% recovery vs only 57+/-3% recovery at pH 7.4). Postischemic edema (2% water gain) was unchanged by pH modification. We conclude that initial reperfusion with the appropriate pH provides an optimal milieu for restoration of cellular metabolism, counteracts the acidosis of ischemia, and improves postischemic left ventricular blood flow, distribution, oxygen uptake, compliance, and performance.
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PMID:Studies on myocardial reperfusion injury. I. Favorable modification by adjusting reperfusate pH. 1 28

Complete global ischemia was produced in 39 dogs by temporary ligation of the aorta. Prior to the ischemic episode, pentobarbital (30 to 45 mg per kilogram of body weight) was administered to 19 of these dogs. The neurological effects of cerebral ischemia episodes lasting 8, 9, or 10 minutes were compared in dogs treated with pentobarbital and those not treated. At 48 hours following the ischemic episode most of the dogs made ischemic for 8 minutes were normal, whereas most animals made ischemic for 10 minutes were dead or comatose. The 9-minute ischemic period resulted in a relatively even distribution of normal and damaged dogs. There were no differences between treated and untreated dogs. Cerebral blood flow, cerebral metabolic rate for oxygen, and various cerebral metabolites were measured in dogs surviving 48 hours. Again, there were no differences between treated and undertreated dogs. We conclude that barbiturates provide no protection in this model of complete global ischemia. This conclusion supports the hypothesis that the likely mechanism of barbiturate protection in models of incomplete ischemia or hypoxia is based on cerebral metabolic depression; such a mechanism would not be expected to be effective in complete global ischemia.
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PMID:No barbiturate protection in a dog model of complete cerebral ischemia. 3 25

We measured rat brain cortex PO2 (PtO2) with gold microelectrodes (tip diameter 5--10 micron) for up to 2 hours after 16 min of transient global brain ischemia with and without thiopental 90 mg/kg infused iv over 60 min beginning at 5 min postischemia. Seventeen rats were immobilized and mechanically ventilated on 1% halothane in oxygen with continuous monitoring of PtO2, ECG, end-expiratory CO2, rectal temperature, and arterial blood pressure. Global ischemia was induced by trimethaphan hypotension to an MAP of about 50 torr and a neck tourniquet inflated to 1500 torr. Postischemia, nine control rats (11 PtO2 measurements) were untreated and eight rats (8 PtO2 measurements) received thiopental 90 mg/kg. Preischemia, PtO2 values in both groups ranged from less than 5--70 torr with values of greatest frequency between 10 and 15 torr. Postischemia, PtO2 in control rats peaked at 45 +/- 8 (SEM) torr at 20 min. In thiopental treated rats, peak PtO2 was 24 +/- 6 torr at 10 min postischemia. Relative frequency histograms of PtO2 revealed that PtO2 in thiopental treated rats was lower (p less than 0.05) between 15 and 30 min postischemia. The magnitude of the decrease in PtO2 between 105 and 120 min postischemia appeared to correlate directly with the absolute preischemic value (i.e., the higher the preischemic PtO2, the greater the decrease in PtO2 postischemia). These results suggest that thiopental administered in large doses in early postischemia does not improve brain oxygenation secondary to a reduction in brain oxygen consumption. The relevance of the correlation between the magnitude of the fall in PtO2 postischemia and the magnitude of the preischemic value is discussed.
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PMID:Postischemic brain oxygenation with barbiturate therapy in rats. 3 43

The indices of central hemodynamics and myocardial contractile function were studied in 35 dogs before and in different periods after the administration of drugs which block beta-receptors: propranolol, pindolol, and talinolol. The drugs blocking the beta-adrenergic receptors were administered against the background of an intact myocardium to 15 dogs and against the background of acute coronary insufficiency to another 15; acute ischemia was induced in 5 dogs to which the drugs were not given. It was established that beta-adrenergic blocking agents have a beneficial effect in the acute stage of myocardial ischemia; they exert a marked influence on the consumption of oxygen by the myocardium, intramyocardial tension, and the contractile capacity and rhythm of the heart. Talinolol produced the most favourable effect.
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PMID:[Effect of blockaders of cardiac beta-adrenergic structures on the central hemodynamics and contractile function of the myocardium in acute experimental coronary insufficiency]. 4 59

In cats air embolism of the brain was produced by injecting 0.6 ml blood foam into the innominate artery proximal to the origin of both common carotid arteries. Air embolism caused transient ischemia of the brain, reaching a maximum within 1 min after injection. Resolution of the air embolism began a few minutes later and was completed within 15 min in the center and within 30 min in the border zone of the main supplying arteries. During this phase tissue perfusion was inhomogenous with reduced flow rates in some areas and reactive hyperemia up to 300% in others. This resulted in venous hyperoxia and a decrease of arteriovenous oxygen difference to as low as 2 ml/100 ml blood. Reactive hyperemia was accompanied by brain swelling and an increase in intracranial pressure from 3.6 +/- 1.2 to 12.3 +/- 2.0 mm Hg. The reason for hyperemia was a decrease of cortical pH which fell from 7.33 +/- 0.03 to 7.03 +/- 0.05, and which caused a dilation of pial arteries up to 260%. Immediately after embolism, the EEG flattened and oxygen consumption decreased. After normalization of flow, oxygen consumption returned to normal, but EEG only partially recovered. Air embolism had little effect on the water and electrolyte content of the brain, and produced very little damage to the blood-brain barrier.
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PMID:Arterial air embolism in the cat brain. 4 47

Circulatory variables and arterial partial pressure for oxygen (PaO2) were compared in 91 anesthetized patients who received infusions of either nitroglycerin (TNG) or nitroprusside (SNP) to induce hypotension for the purpose of decreasing intraoperative blood loss. At comparable systolic arterial blood pressures, the mean and diastolic arterial blood pressures were significantly higher with TNG. Electrocardiographic changes suggestive of ischemia occurred in 18 patients who received SNP, whereas none were detected in patients given TNG. Both drugs significantly decreased PaO2 and rate-pressure product, an indirect index of myocardial oxygen consumption. No untoward response to TNG occurred. No clinical evidence of myocardial infarction, renal damage, or cerebral vascular complication was encountered in the postoperative period in any patient. Thus, TNG is an effective hypotensive drug that may prove superior to currently available agents.
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PMID:Nitroglycerin as a hypotensive drug during general anesthesia. 9 6


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