Effect of Nucleosides on Acute Left Ventricular Failure in the Isolated Dog Heart

Buckley, N. M.; Tsuboi, Kenneth K.; Zeig, Norman J.

doi:10.1161/01.res.7.6.847

Cited by 37 publications

(14 citation statements)

References 15 publications

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“…Buckley et al (1959) used an isolated canine left ventricle preparation to demonstrate that exogenous inosine exerts a positive inotropic effect after the onset of acute left ventricular failure. The inotropic effect of inosine occurred independent of heart rate, chamber size, or coronary supply.…”

Section: Discussionmentioning

confidence: 99%

Inosine: a protective agent in an organ culture model of myocardial ischemia.

Goldhaber¹,

Pohost²,

Kloner³

et al. 1982

Circulation Research

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SUMMARY. Fetal mouse hearts in organ culture provide a model of ischemic-like injury in which the myocardial protective effect of pharmacological agents can be studied independent of blood flow. To investigate the potential protective effect of a diffusable purine under ischemic-like conditions, we used 4 mM inosine in fetal mouse heart organ cultures deprived of oxygen and oxidizable substrates for 1-10 hours. We studied hearts (n = 258) immediately after simulated ischemia (early) and after a 20-hour recovery period (late), by utilizing three indices of myocardial viability. Thallium-201 accumulation is an early marker of myocardial viability during injury, whereas the percentage of lactic dehydrogenase release from hearts to culture medium and the percentage of irreversibly injured myocytes assessed by planimetry of midventricular histological sections are late markers, used after recovery from injury. At 10 hours of injury, thallium-201 accumulation was 38% greater in inosine-supplied hearts, 3.50 ± 0.16 vs. 2.54 ± 0.08 (counts/min per mg wet weight)/(counts/min per jul medium) (mean ± SEM) (P < 0.001). After recovery from 10 hours of injury, lactic dehydrogenase release was 29% less in inosine-supplied hearts, 35 ± 3% vs. 49 ± 3% (P < 0.001). After recovery from 8 hours of injury, the percentage of histologically irreversibly injured tissue was 23% less in inosine-supplied hearts, 60 ± 7% vs. 78 ± 3% (P < 0.05). These data indicate that inosine has a protective effect on fetal mouse myocardium during simulated ischemia and suggest that inosine deserves further evaluation. (Circ Res 51:181-188, 1982)

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Section: Discussionmentioning

confidence: 99%

Inosine: a protective agent in an organ culture model of myocardial ischemia.

Goldhaber¹,

Pohost²,

Kloner³

et al. 1982

Circulation Research

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“…Additionally, uridine has been used in the treatment of convulsions (Dwivedi and Harbison, 1975;Roberts, 1973) and liver disease (Elrick et al, 1962). Experimental research indicate that uridine may also be useful in the treatment of ischaemia (Aussedat, 1984;Buckley et al, 1959).…”

Section: Introductionmentioning

confidence: 99%

Rapid determination of rat plasma uridine levels by HPLC‐ESI‐MS utilizing the Captiva™ filter plates for sample preparation

Williams¹,

Palandra²,

Shobe³

2003

Biomedical Chromatography

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A rapid, accurate and precise HPLC-ESI-MS method for the determination of rat plasma uridine concentrations was developed and is described here. Sample preparation involves methanol precipitation of plasma proteins in a 96-well Captiva protein precipitation filter plate. A clear extract is drawn through the filter plate with vacuum, followed by evaporation of the extract and subsequent reconstitution prior to chromatography on a reversed-phase column with an aqueous mobile phase [0.1% (v/v) glacial acetic acid]. Detection was accomplished by positive-ion electrospray ionization mass spectrometry. A calibration curve ranging in concentration from 0.78 to 25 microM was constructed by best-fit, 1/x weighting linear regression analysis of the calibration standard concentrations vs peak height ratios of analyte with internal standard. The correlation coefficient was >0.995. The overall assay accuracy as shown by the back-calculated concentrations of the calibration curve ranged from 96.6 to 103% with RSD ranging from 4.5 to 20%. While this assay method was developed for the determination of uridine in rat plasma, it could be readily adapted for determination of uridine in plasma from other species, such as human.

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“…In particular, the work of Rubio and Berne (28) has led to the suggestion that the purine nucleoside adenosine may be important in the regulation of coronary blood flow. Further more, several studies have demonstrated that a variety of purine and pyrimidine nucleosides and nucleobases act as inotropic agents in isolated hearts (4,5,7,21). The purine nucleoside inosine acts as a positive inotropic agent in the isolated heart, and interest in the effects of this derivative on the in situ heart has been especially high.…”

Section: Introductionmentioning

confidence: 99%

Effect of Inosine on Ventricular Regional Perfusion and Infarct Size after Coronary Occlusion

Devous¹,

Jones²

1979

Cardiology

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In 16 dogs inosine was infused at 0.5 mmol/min i.v. for 5 min beginning 15 min after coronary occlusion. Tracer microspheres were used to estimate flow in subepicardium and subendocardium of nonischemic, central ischemic, and borderline ischemic muscle. Estimates of flow before occlusion, 5 min after occlusion, during inosine infusion, 30 min after infusion and 60 min after infusion were obtained. Coronary occlusion reduced flow in the central ischemic regions by 75-95%. The reduction in flow was greatest in subendocardium. In the borderline regions subendocardial flow was reduced by 30% while subepicardial flow was unaffected. The major effects of inosine were seen in nonischemic and borderline ischemic regions. Flow in borderline subendocardium returned to its pre-occlusion value, and flow in nonischemic myocardium increased by approximately 60-80%. However, only in the ischemic regions was the increase in flow sustained for the entire 60 min. In 20 dogs infarct size was determined using nitro blue tetrazolium stain. In 10 controls infarct size was 20.1%, while in 10 inosine-treated dogs infarct size was 15.2% of left ventricular weight (p < 0.01). Thus, following coronary occlusion inosine infusion was associated with an increase in perfusion of ischemic myocardium and a reduction in infarct size.

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Effect of Nucleosides on Acute Left Ventricular Failure in the Isolated Dog Heart

Cited by 37 publications

References 15 publications

Inosine: a protective agent in an organ culture model of myocardial ischemia.

Inosine: a protective agent in an organ culture model of myocardial ischemia.

Rapid determination of rat plasma uridine levels by HPLC‐ESI‐MS utilizing the Captiva™ filter plates for sample preparation

Effect of Inosine on Ventricular Regional Perfusion and Infarct Size after Coronary Occlusion

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