Brief Periods Of Myocardial Ischemia Research Articles

810-1 Enhanced Inflammatory Acute Phase Response After Percutaneous Coronary Angioplasty in Patients with Unstable Angina

Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, are independent predictors of short-term prognosis in patients (pts) with unstable angina (UA). The causes of the acute phase response in UA, however, are still unknown. Percutaneous transluminal coronary angioplasty (PTCA) is an useful model for the assessment of the effects of plaque disruption and myocardial ischemia on the acute phase response. Serum levels of CRP were measured in 21 pts with chronic stable angina (SA) (G 1) and in 22 pts with UA refractory to maximal medical treatment (G2), undergoing single-vessel PTCA. Venous blood samples were taken immediately before PTCA and 6, 24, 48, 72 hours after the end of the procedure. CRP values are expressed as median and range. Before PTCA, CRP was elevated (> 3 mg/l) in 2/21 G1 pts (10%) and in 16/22 G2 pts (73%) (p < 0.001): it was 2.4 (2–4.4) mg/l in Gl and 8 (2.4–29) mg/l in G2 (p < 0.001). After PTCA, CRP increased to a peak value of 2.6 (2–16.4) mg/l 38 ± 13 hrs after the procedure in Gl, and to a peak value of 19.9 (2.8–49.4) mg/l 32 ± 14 hrs after the procedure in G2 (p < 0.001. G1 vs G2). A significant increase in CRP after PTCA, defined as an increase > 50% the basal values, was observed in 8/21 Gl pts and in 16/22 G2 pts (p < 0.05). The percentage increase of CRP after PTCA was higher in G2 than in Gl (180 ± 239%, range 0–925% vs 118 ± 176%, range -13–489%, p < 0.05). No difference in coronary stenosis severity before PTCA (84 ± 9% vs 89 ± 8%), residual stenosis (30 ± 7% vs 29 ± 10%), number of ballon inflations (6 ± 3.4 vs 5.3 ± 3.2), total inflation time (365 ± 202 vs 413 ± 197 sec) and mean inflation pressure (5 ± 0.9 vs 5 ± 1 atm) was found between Gl and G2 pts. Our study shows that the plaque disruption and the brief periods of myocardial ischemia caused by PTCA elicit a variable individual inflammatory acute phase response, that is greater in UA compared to SA pts. These data suggest a higher inflammatory responsiveness in patients with UA, that may playa pathogenetic role in acute coronary syndromes, and help explaining the higher rate of acute complications typically observed in patients with unstable angina undergoing PTCA.

915-81 Release of Endothelin After Severe Short Lasting Myocardial Ischemia

Endothelin (ET) is an endothelium-derived vasoactive peptide, its possible contribution to myocardial ischemia and infarction is not yet well understood. was to elucidate whether a brief period of myocardial ischemia (CI) not leading to myocardial infarction may increase plasma ET levels and to determine the kinetics of a possible ET release. A coronary sinus lactate study with incremental atrial pacing was performed in 16 patients (pts) with obstructive coronary artery multivessel disease (CAD). A Zucker-catheter was positioned in the distal coronary sinus for incremental atrial pacing (100–160 bpm) and lactate sampling. ET was measured by a radio-immuno-assay 1100% ET-1, 52% ET-2, 96% ET-3, 7% Big-ET, Nichols Institute). ET, cardiac troponin-T (TnT, Boehringer Mannheim) and creatine phosphokinase (CPK) samples were withdrawn from the coronary sinus (CS) and a peripheral vein (PV) before and at time 1, 5, 10, 30, 45 min, 1, 2, 3, 6 h after pacing. Significant ST depressions in the 12-lead ECG after pacing was a further criterion for CI. A comparison to the results of a control group (CG, n = 13) without heart disease and statistical analysis was done. In CAD pacing stress induced a CI in all pts (duration 6.1 ± 1.2 min). The mean cardiac lactate production was 143.9 ± 19.3% compared with the arterial lactate concentration, all pts suffered from typical angina pectoris, significant ST depressions of 0.32 ± 0.11 mV were found in 14/16 pts. All pts developed pathological elevated ET concentration, whereas the levels in the CG were within the limits of normal (p < 0.003). The mean ET concentrations increased from 5.0 pg/ml in CS and PV before pacing to 10.9 pg/ml in CS and 8.9 pg/ml in PV at 1 min after the end of pacing. The concentrations further remained elevated within 1 h after pacing with higher levels in CS than in PV due to a persisting cardiac release of ET, ET concentrations dropped to the limits of normal (2.3–5.3 pg/ml) after 1 h with identical levels in CS and PV In both groups TnT and CPK were not elevated, no signs of CI were detected in the CG. A short lasting severe myocardial ischemia without myocardial infarction was followed by a significant ET release for 1 h reaching 218% of the base line concentration in CS and 178% in PV respectively. The higher ET levels in CS compared to PV indicate, that the ET release is of cardiac origin.

Regional and Systemic Platelet Function Is Altered by Myocardial Ischemia-Reperfusion.

Background: Myocardial reperfusion after short durations of ischemia causes prolonged contractile dysfunction (myocardial stunning). Recently it has also been suggested that ischemia-reperfusion results in impaired coronary endothelial function. Since platelet function is, in part, regulated by an intact functioning endothelium, platelet function could be expected to change during ischemia-reperfusion. However, the effect of ischemia and reperfusion on regional and systemic platelet function is unknown. The purpose of this study was to determine the effect of a brief period of myocardial ischemia followed by reperfusion on regional and systemic platelet function. Methods: Fourteen swine in an open-chest model underwent left anterior descending coronary artery (LAD) occlusion for 15 minutes followed by 120 minutes of reperfusion. Platelet aggregability in response to 5 µM ADP was determined simultaneously in the femoral (systemic; N = 14) and great cardiac (regional; N = 9) venous blood at baseline, during occlusion, and at 40 and 90 minutes after reperfusion. LAD blood flow and regional myocardial function were determined by standard methods. Results: Hemodynamics remained stable in all animals. During LAD occlusion platelet aggregability, increased only in the regional coronary circulation (126% of baseline, p =.0001). At 40 minutes of reperfusion systemic platelet aggregahility decreased (86% of baseline, p =.0001) and subsequently increased at 90 minutes at reperfusion in both the systemic (127% of baseline, p =.0001) and regional circula. tions (156% of baseline, p =.0001). Ischemia was evident by the absence ofdistal LAD flow during occlusion that returned during reperfusion and a typical response ofmyocardial stunning in each animal (stunning time = 47.7 +/- 5.2 minutes). Conclusions: This study demonstrates that platelet function is not static during ischemia-reperfusion. Instead, during ischemia regional platelet aggregability is increased. Systemic and regional platelet aggregability also increase during myocardial reperfusion. The mechanism of these responses is unknown but may be related to regional endathelial dysfunction created by ischernia. The response observed could also be explained by the release of proaggregatory mediators in the connary and/or systemic circulation during ischemia-reperfusion. The relative hyeraggregability observed following reperfusion may be relevant for further investigations of coronary artery reocclusion occurring after the relief of myocardial ischemia.

The effect of ischemic preconditioning on nucleotide metabolism and function of rat heart after prolonged cold storage.

Experimental data suggests that brief periods of myocardial ischemia followed by reperfusion induced by coronary artery occlusion or global ischemia enhances myocardial tolerance to subsequent, more prolonged ischemic episodes (Ischemic Preconditioning)1. However, the effect of ischemic preconditioning on the contractility and metabolism of the heart subjected to prolonged cold storage induced by a single use of cold cardioplegia as in clinical heart transplantation has not been determined. In this study we evaluated the effect of 5 min ischemia and 10 min reperfusion on the recovery of myocardial mechanical function and metabolism following 6 hours of 4°C preservation using an isolated rat heart preparation.

Impairment of myocardial vascular responsiveness after transient myocardial ischemia and reperfusion

Coronary vascular responses after brief periods of myocardial ischemia are impaired. Whereas some studies suggest that the ischemic insult selectively depresses endothelium-dependent vasodilator mechanisms, other studies indicate that even responses to direct vascular smooth-muscle relaxants such as adenosine may be decreased. This study was undertaken to measure regional myocardial blood flow (RMBF) responses to adenosine (a direct coronary vasodilator) and serotonin (an indirect, endothelium-dependent vasodilator) in myocardium subjected to regional ischemia followed by reperfusion. Temporary regional ischemia was achieved by 20 minutes of occlusion of the left anterior descending coronary artery (LAD) followed by 20 minutes of reflow in 10 open-chest anesthetized dogs. In the left circumflex coronary artery (LCX) territory, which served as a nonischemic control, RMBF (measured with radioactive microspheres) increased significantly in response to left atrial infusions of adenosine (1.29 ± 0.27 to 3.89 ± 2.15 ml/min/gm; p < 0.001) and serotonin (1.29 ± 0.27 to 3.29 ± 1.49 ml/min/gm; p < 0.001) and the percent reduction in coronary vascular resistant (%ΔCVR) was comparable for these two pharmacologic probes (65% ± 26% ± 19%; difference not significant [NS]). In contrast, in the myocardium supplied by the LAD, which was subjected to ischemia followed by reperfusion, the augmentation of RMBF by adenosine (1.07 ± 0.29 to 1.82 ± 1.35 ml/min/gm; p < 0.001) and serotoinin (1.07 ± 0.29 to 2.37 ± 1.21 ml/min/gm; p < 0.001) was blunted. The absolute increase in RMBF after adenosine infusion was significantly less than that for serotonin infusion ( p < 0.001), and the %ΔCVR also was significantly less (43% ± 24% vs 56% ± 22%; p < 0.001). Thus despite comparable values for heart rate (147 ± 21 vs 146 ± 19 beats/min; NS), mean arterial pressure (90 ± 20 vs 101 ± 26 mm Hg; NS),cardiac output (3.2 ± 1.0 vs 3.5 ± 1.41/min; NS), and %ΔCVR in the control LCX territory during left atrial infusions of adenosine and serotonin, in the previously ischemic LAD bed the vasodilator response to adenosine was significantly more depressed than the vasodilator response to serotonin. In conclusion, a brief period of regional myocardial ischemia followed by reperfusion, insufficient to cause structural alterations in the microvasculature, causes a profound depression of vasodilator responses to adenosine and serotonin. Contrary to the notion that ischemia selectively depresses endothelium-dependent vasodilation, RMBF responses to serotonin, a putative indirect vasodilator, were better preserved than were RMBF responses to adenosine, a direct smooth-muscle relaxant. The complex interrelation between ischemia followed by reperfusion and the functional vasodilator responses of the microvasculature (at least with respect to these two pharmacologic probes) is more complex than previously recognized.

Time course of electrical fibrillation threshold during brief periods of myocardial ischemia and the genesis of fibrillation: Role of calcium

Time course of electrical fibrillation threshold during brief periods of myocardial ischemia and the genesis of fibrillation: Role of calcium

Expression and Immunohistochemical Localization of Heat‐Shock Protein‐70 in Preconditioned Porcine Myocardium

Brief periods of ischemia not only cause a long lasting (hours to days) myocardial contractile dysfunction (stunning) but also increase the tolerance for irreversible damage during a subsequent ischemic episode, a phenomenon called ischemic preconditioning.1J Heat-shock proteins, in particular HSP-70, have been postulated in myocardial protection against irreversible damage due to i~chemia .~ It is known that in vivo as well as in vim, metabolic stressors (e.g., ischemia) and heat lead to the rapid synthesis of 70 kD heat-shock protein (HSP-70) family.3.4 However, the cellular distribution and its potential role in ischemic preconditioning have not yet been well established. Brief periods of myocardial ischemia in rabbits also cause a rapid expression of HSP-70, which is detectable at the protein level within 2 h.4 Recently, we have shown that porcine myocardium responds to ischemia and repehsion by inducing a battery of genes.5-7 In this study, we examined the expression pattern and cellular distribution of HSP-70 in a porcine model of myocardial stunning and preconditioning achieved by two cycles of 10 min of ischemia and 30 min of reperfusion followed by additional 90 and 180 min of reperfusion.

Effect of Moxonidine on Arrhythmias Induced by Coronary Artery Occlusion and Reperfusion

The aim of the present study was to investigate the influence of moxonidine, a representative of I1-imidazoline-receptor agonist, on arrhythmias induced by myocardial ischemia or reperfusion. Acute myocardial infarction was produced by tightening a previously placed loose silk loop around the coronary artery in conscious rats. Moxonidine (0.01, 0.03, or 0.10 mg/kg i.v., 10 min before coronary ligation) significantly decreased the incidence of ventricular tachycardia during the first 15 min of infarction (70 versus 100% in controls), and the number of animals that survived without developing any arrhythmia was increased (15, 20, and 25%, respectively, versus 0%). Reperfusion-induced arrhythmias were produced by releasing a snare after 6 min of myocardial ischemia in anesthetized, artificially ventilated rats. Reperfusion rapidly induced severe dysrhythmias in all of the control animals. Moxonidine pretreatment (0.03 and 0.10 mg/kg) decreased the incidence of ventricular fibrillation (25 and 30% versus 64%) and increased the number of animals that survived without developing any arrhythmia (20 and 25% versus 0%). We conclude that moxonidine offers significant protection against the development of arrhythmias induced by acute regional myocardial ischemia in conscious rats. Moxonidine pretreatment also provides a beneficial effect during reperfusion-induced arrhythmias that appear after a brief period of myocardial ischemia.

Endothelin is released from the porcine coronary circulation after short-term ischemia.

Endothelin (ET) is increased in plasma after myocardial infarction. Whether brief periods of myocardial ischemia not leading to myocardial infarction also increase plasma ET is not known. The purpose of the present study was to examine cardiac ET balance in association with a 10-min LAD occlusion followed by reperfusion. Venous blood was selectively sampled from the transiently ischemic myocardium using a shunt between the anterior interventricular vein and the right atrium in eight pentobarbital-anesthetized pigs. Flow in the shunt was measured with a Doppler flow probe. Arterial blood was drawn from the aortic arch. Plasma ET was measured using an ET [1-21]-specific 125I assay system. This assay system has no cross-reactivity with big ET. A net cardiac ET uptake of 0.7 (0.3-1.4) fmol min-1 g-1 (median, 95% confidence interval) in the control period shifted to a net release during the first 10 min of reperfusion. The release reached a maximum of 2.8 (0.4-6.0) fmol min-1 g-1 after 1.5 min of reperfusion. Cardiac venous ET concentration increased from 3.4 (2.5-4.8) to 4.4 (3.6-6.9) and 4.4 (3.6-6.6) fmol ml-1 at 1.5 and 5 min of reperfusion, respectively (p < 0.001 for both). Arterial ET concentration decreased from 4.8 (3.9-6.1) to 2.7 (2.4-4.3) fmol ml-1 at 10 min of reperfusion (p < 0.001). ET is released from the porcine heart for several minutes during reperfusion after a brief coronary artery occlusion.

Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors.

A brief period of myocardial ischemia can result in an increased resistance to subsequent, more severe episodes of ischemia. Recent studies have indicated that activation of adenosine A1-receptors may mediate this preconditioning effect. It is also known that A1-activation can lead to ATP-sensitive potassium channel (KATP) opening via a G(i) protein-mediated effect. Thus, we determined whether the KATP blocker glyburide could abolish preconditioning or the protective effects of A1-receptor activation. Anesthetized dogs were subjected to 5 minutes of left circumflex coronary artery (LCx) occlusion (or sham) followed by 10 minutes of reperfusion. The hearts were then subjected to 60 minutes of LCx occlusion and 5 hours of reperfusion. Glyburide (5 micrograms/kg/min) or vehicle was given directly into the LCx 20 minutes before preconditioning or sham preconditioning. Preconditioning resulted in a significantly reduced infarct size compared with nonpreconditioned animals. Glyburide abolished the protective effect of preconditioning. To establish a link between KATP and A1-receptor activation, the effect of the A1-agonist R-PIA with or without glyburide on infarct size was determined. R-PIA (0.4 microgram/kg/min, directly into the LCx) significantly reduced infarct size, and this protective effect was abolished by glyburide. None of the treatments described above had a significant effect on peripheral hemodynamic status or myocardial blood flow. Preconditioning may be mediated by KATP activation, and this may be linked to A1-receptor stimulation.

Transient myocardial wall motion abnormalities in a child: The phenomenon of “stunning”

Reversible depression of myocardial function following brief periods of myocardial ischemia has been shown to occur in both animal models and humans.l, s Radionuclide angiocardiography, contrast echocardiography, stress echocardiography, and cineangiography have been used to study the extent and severity of myocardial dysfunction following episodes of ischemia or infarction.2-5 To our knowledge, transient wall motion abnormalites have not been visualized in children. We report the observation of extensive anteroseptal wall motion abnormalities after tonsillectomy and adenoidectomy; the abnormalities completely resolved in 4 days and were not associated with identifiable coronary artery abnormalities. A &year-old white girl underwent elective tonsillo-adenoidectomy for recurrent tonsillitis with tonsillar enlarge-

Energy formation during brief periods of myocardial ischemia and subsequent reperfusion

Energy formation during brief periods of myocardial ischemia and subsequent reperfusion

Effects of nitroglycerin and nifedipine on coronary and systemic hemodynamics during transient coronary artery occlusion

Nitroglycerin (NTG) and nifedipine (NIF) have the potential to augment coronary blood flow in addition to reducing peripheral determinants of myocardial oxygen demand as a synergistic protective mechanism during ischemia. To examine these effects, systemic and coronary hemodynamic responses were measured continuously before and during brief periods of myocardial ischemia induced by left anterior descending coronary balloon occlusion in 26 patients undergoing angioplasty (PTCA). Data were compared for two matched occlusion periods, one control and one “drug” occlusion. In 17 patients (NTG group), 200 μg of intracoronary NTG was given immediately before coronary occlusion. In nine patients (NIF group), 10 mg of sublingual NIF was given 15 minutes before the “drug” occlusion. NTG significantly but transiently reduced mean arterial pressure (91 ± 11 to 82 ± 15 mm Hg, p < 0.05) and augmented basal coronary blood flow (95 ± 38 to 127 ± 54 ml/min, p < 0.05) but did not alter great vein blood flow (59 ± 29 vs 61 ± 29 ml/min) or coronary occlusion pressure (25 ± 7 to 24 ± 7 mm Hg) during ischemia. NIF significantly reduced systolic, diastolic, and mean arterial pressure (119 ± 21 to 95 ± 8 mm Hg, p < 0.001) and heart rate-pressure product from control. NIF maintained basal great vein blood flow (125 ± 41 to 106 ± 57 ml/min) during reduced myocardial oxygen demand, but did not affect great vein blood flow (73 ± 29 to 79 ± 37 ml/min) or coronary occlusion pressures during ischemia. Neither agent prolonged the time to ischemic ST segment alteration after the 50 to 60 second coronary flow occlusion periods. These data suggest that during the initial minutes of myocardial ischemia due to coronary occlusion, neither the coronary nor peripheral hemodynamic effects of the two vasodilators significantly improved regional coronary blood flow responses of ECG signs of myocardial ischemia. During PTCA, the beneficial effects of these agents most likely occur through mechanisms such as spasmolytic action, or indirectly by reduction of myocardial oxygen demand, more than directly augmenting coronary blood flow or collateral supply.

Regulation of coronary resistance vessels and large coronary arteries

There is now considerable evidence for α-adrenergic regulation of coronary resistance vessels and large coronary arteries based on studies of chronically instrumented, conscious animals. Infusion of norepinephrine at low doses causes reduction of coronary blood flow with a slight increase in arterial pressure, indicating intense coronary vasoconstriction. This coronary constrictor response was reversed to coronary vasodilation with infusion of norepinephrine after α-adrenergic blockade. Stimulation of α 1- and α 2-adrenergic receptors with phenylephrine and B-HT 920, respectively, also increased calculated coronary vascular resistance in the conscious animal. These effects were eliminated by selective α 1-adrenergic blockade with prazosin and by selective α 2-adrenergic blockade with rauwolscine. Stimulation of the carotid chemoreceptor reflex elicits a period of intense coronary vasoconstriction, characterized by a decrease in coronary blood flow despite increased arterial driving pressure. This response was eliminated by prior α-adrenergic blockade or a combination of cardiac sympathetic denervation and adrenalectomy. Using chronically implanted ultrasonic crystals to measure the epicardial coronary diameter instantaneously and continuously in conscious dogs, marked vasodilation of the large coronary arteries was observed with administration of nitroglycerin or calcium-channel antagonists; in contrast, activation of α-adrenergic receptors with methoxamine induced substantial constriction, characterized by a reduction in coronary artery diameter in the face of elevated distending pressure. The regulation of large coronary arteries is further complicated by the fact that these vessels are responsive to changes in myocardial metabolic demands and coronary blood flow. This was demonstrated by examining responses to brief periods of myocardial ischemia, which induced intense reactive dilation, i.e., dilation of the large coronary artery immediately after the reactive hyperemia response. The dilation of the large coronary artery was not observed after brief periods of myocardial ischemia, when the marked increase in coronary blood flow (reactive hyperemia) was prevented. These findings suggest that coronary artery vasconstriction may be more intense under conditions in which blood flow cannot increase, for example, in the presence of severe stenoses.

Creatine kinase of heart mitochondria. The progressive loss of enzyme activity during in vivo ischemia and its correlation to depressed myocardial function.

It is now appreciated that mitochondrial creatine kinase (CKm) may play an important role in heart high-energy phosphate metabolism and that this isozyme is solubilized in vitro by dilute solutions of Pi. Since an increase in cellular Pi is known to occur with even brief periods of myocardial ischemia, we investigated the relationship between CKm activity and myocardial performance in rabbit hearts subjected to total global ischemia. CKm activity is expressed as a ratio to mitochondrial malate dehydrogenase (MDHm), a stable marker enzyme. A significant decline in this ratio was observed after only 10 min of ischemia, a time prior to changes in total homogenate creatine kinase activity. After 60 min of ischemia, the CKm/MDHm ratio was depressed by more than 70%. Since there was no restoration of activity following 30 min of reperfusion, we correlated changes in enzyme activity to contractile dysfunction following variable periods of total ischemia. The data showed a close correlation between the decline in the CKm/MDHm ratio and the reduction in performance, measured as left ventricular developed pressure. No correlation was observed between State 3 respiratory rates and performance. Using KCl arrest at 27 degrees C or hyperthermic ischemia at 40 degrees C, the CKm/MDHm ratio consistently correlated to the degree of postischemic functional depression, independent of the duration of ischemia. Isoenzyme electrophoresis failed to detect soluble CKm activity in the postischemic supernatant. Therefore, CKm activity appears to be altered rapidly and irreversibly by ischemia. The implications of these observations on the integration of myocardial high-energy phosphate metabolism are discussed.

Prolonged abnormalities of myocardium salvaged by reperfusion.

The purpose of this study was to determine if biochemical, functional, and ultrastructural abnormalities persist in nonnecrotic postischemic myocardium salvaged by coronary reperfusion. Anesthetized dogs were subjected to 15 min of occlusion of the left anterior descending (LAD) coronary artery followed by 3 days of reperfusion. Biopsies were obtained for measurement of adenosine 5'-triphosphate (ATP) and creatine phosphate (CP) nmol/mg protein), and regional function was evaluated using sonomicrometry. Myocardial ATP concentration after 15 min of occlusion was 37 +/- 1 nmol/mg cardiac protein in nonischemic subendocardium and 19 +/- 2 nmol/mg in ischemic subendocardium. After the hearts underwent 90 min and 72 h of reperfusion, ATP remained significantly depressed in reperfused subendocardium with values of 25 +/- 5 and 29 +/- 2 nmol/mg, respectively (P less than 0.05 and P less than 0.01 compared with the nonischemic zone in which ATP remained normal). CP levels fell during ischemia but returned to normal by 90 min of reperfusion. Percent systolic shortening of myocardial segments fell from +18 +/- 1% (active shortening) to -13 +/- 2% (passive lengthening) during ischemia and was still significantly depressed at +11 +/- 1% (P less than 0.05 vs. preocclusion) at 72 h of reperfusion. Histological examination showed no necrosis, but ultrastructural abnormalities were present. Therefore brief periods of myocardial ischemia are not associated with necrosis but result in functional, biochemical, and ultrastructural abnormalities, which are present for at lest 3 days after coronary reperfusion.

Analysis of purines and their nucleosides by the reverse phase partition mode of high pressure liquid chromatography.

Although the analysis of nucleotides in blood is now being carried out routinely by high pressure liquid chromatography (HPLC) (1–4), and work is in progress to determine alterations casued by various disease states of free nucleotide concentrations in physiological fluids and cell extracts (5,6), less attention has been paid to free nucleoside levels in cells. Recent investigations, however, have focused attention on methylated nucleosides in cells as biological markers in cancer (7,8). Moreover, nucleoside concentrations are thought to be important in cardiac disease and birth defects. The intracellular level of adenosine, one of the physiological regulators of coronary blood flow, has been found to increase in cardiac hypertrophy and after brief periods of myocardial ischemia and hypoxia (9,10). In abnormalities in purine metabolic pathways caused by disease, the concentrations of purine bases and/or their nucleosides often are involved. For example in patients with adenosine deaminase deficiency, it has been observed that excess adenosine in cultured mammalian cells is toxic (11) and it has been postulated that accumulated adenosine is associated with severe immunological defects in children (12).KeywordsXanthine OxidaseHigh Pressure Liquid ChromatographyPurine BasePotassium Dihydrogen PhosphatePartition ModeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.