Effect of ribose on cardiac adenine nucleotides in a donor model for heart transplantation.

Preservation time of explanted hearts is short. Cardiac function after transplantation declines dramatically in hearts that have been preserved for more than 4 to 6 hours. This has been linked to a critical decrease in high energy phosphates (HEP) after explantation. Ribose has previously been shown to stimulate HEP synthesis and to improve cardiac function. In this study, ribose was infused into 20 rats for 24 hours continuously before explantation (donor treatment) and also added to the solutions used for preservation. Saline was used in the control group. Myocardial tissue biopsies were taken after 24h of infusion and after 4h of preservation. High energy phosphates were determined by HPLC. Adenosine triphosphate content (ATP), energy charge and total adenine nucleotides (TAN) were significantly lower after 4h of preservation in both the ribose-treated and the control group compared to hearts before preservation. The difference in mean ATP concentrations between the 4 hours preserved ribose group and the control group was not significant. Single case analysis however revealed a minimum ATP level of 12.3 micromol/g dry weight in 10 ribose treated hearts whereas 2 out of 11 control hearts showed ATP levels below 10 micromol/g dry weight. - This study supports the hypothesis that ribose treatment is capable of maintaining ATP at a higher level in preserved rat hearts. Donor treatment and metabolic support with ribose during organ preservation may be suitable to prolong preservation time of donor hearts.

Volumes and Na+/H+ antiporter activity of lymphocytes in patients with congestive heart failure.

Previous studies in patients with congestive heart failure (CHF) treated with diuretics and/or digoxin have shown abnormalities of cellular volume and electrolytes in biopsies of skeletal muscle. These abnormalities seem to play an important role with regard to the dysregulation of peripheral vascular resistance and characteristic clinical features of CHF, for example, muscular weakness. This study assessed the effect of angiotension-converting enzyme (ACE) inhibitor therapy on cell volume and cell volume regulation in patients with CHF. Cell diameters of human mononuclear leukocytes (HML) were determined electronically by a Coulter Counter. Cell diameters for 19 patients with decreased left ventricular ejection fraction (determined via levocardiography) on therapy with ACE inhibitors (group 1) were compared to those of HML from patients on diuretics alone (group 2, n = 16). The activity of the Na+/H+ antiporter was determined by cell swelling in isotonic propionate. The control group consisted of 20 normal, age- and sex-matched volunteers. HML diameters were significantly increased from 7.16 +/- 0.07 in normals to 7.24 +/- 0.08 microns (group 1; P < 0.01) and 7.23 +/- 0.11 microns (group 2; P < 0.05), indicating an abnormal regulation of cell volume. There were no statistically significant correlations between the individual ejection fraction or digoxin therapy and average cell diameters. In both patient groups ethylisopropylamiloride-sensitive swelling rates were normal compared to the control group indicating a normal activity of the Na+/H+ antiporter. In conclusion, increased cell sizes reflect a structural change in HML rather than a rapidly reversible functional abnormality which was not affected different by ACE inhibition and diuretic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of therapeutic ribose levels on human lymphocyte proliferation in vitro.

Ribose has been used successfully in the treatment of ischemic heart disease and muscular enzyme deficiencies, and its administration also facilitates the diagnosis of coronary artery disease by influencing thallium-201 scintigraphy. Concerns about the safety of ribose therapy have been triggered by reports about inhibitory effects of ribose on cell proliferation in vitro. This study examines possible side effects of ribose on human lymphocytes. Unstimulated and mitogen-stimulated human lymphocytes were incubated with ribose concentrations associated with high-dose oral administration, i.e., 3.5 mM, and with two- (7 mM) and tenfold (35 mM) higher concentrations. Cell cultures with matching glucose concentrations served as controls. Incorporation of [3H]thymidine into cells was used to measure cell proliferation. No significant inhibition of human lymphocyte proliferation in vitro was observed in mitogen-stimulated cells. Unstimulated cultures showed significant inhibition only at 35 mM ribose. It is concluded that ribose plasma levels associated with high-dose oral administration do not inhibit human lymphocyte proliferation in vitro. No evidence was found that short-term ribose therapy is harmful to human lymphocytes.

Effects of ribose on exercise-induced ischaemia in stable coronary artery disease.

There is no established treatment specifically aimed at protecting or restoring cardiac energy metabolism, which is greatly impaired by ischaemia. Even after reperfusion, myocardial content of ATP remains low for more than 72 h. Long-term post-ischaemic dysfunction and irreversibility of ischaemic damage have been associated with low ATP content. Evidence that the pentose sugar ribose stimulates ATP synthesis and improves cardiac function led us to test the possibility that ribose increases tolerance to myocardial ischaemia in patients with coronary artery disease (CAD). 20 men with documented severe CAD underwent two symptom-limited treadmill exercise tests on 2 consecutive days; we postulated that the ischaemia induced might bring about changes in ATP metabolism lasting for several days. Patients whose baseline tests showed reproducibility were randomly allocated 3 days of treatment with placebo or ribose 60 g daily in four doses by mouth. Exercise testing was repeated after treatment on day 5. At that time mean (95% confidence interval) treadmill walking time until 1 mm ST-segment depression was significantly greater in the ribose than in the placebo group (276 [220-331] vs 223 [188-259] s; p = 0.002). The groups did not differ significantly in time to moderate angina. In the ribose-treated group the changes from baseline to day 5 in both time to ST depression and time to moderate angina were significant (p less than 0.005), but these changes were not significant in the placebo group. In patients with CAD, administration of ribose by mouth for 3 days improved the heart's tolerance to ischaemia. The presumed effects on cardiac energy metabolism offer new possibilities for adjunctive medical treatment of myocardial ischaemia.

Lack of association of migraine with coronary vasospasm.

Previous reports have found an association between coronary vasospasm and migraine. It has been speculated that migraine and variant angina might be manifestations of a generalized vasospastic disorder. To investigate this hypothesis, 74 patients with frequent attacks of migraine were studied using 24-h continuous ambulatory electrocardiography to identify the presence of coronary vasospasm. Control groups consisted of 19 patients with tension headaches, and 38 healthy individuals. All subjects were free of heart disease. One patient in the migraine group and one patient in the control group had symptomless episodes of ST-segment depression not indicative of coronary vasospasm. Our data do not support the hypothesis that migraine and variant angina are components of a generalized vasospastic disorder.