Treatment Heart Failure: D-Ribose

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Introduction to D-Ribose

D-Ribose scientific review

D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study

Omran H, Illien S, MacCarter D, St Cyr J, Luderitz B.

Patients with chronic coronary heart disease often suffer from congestive heart failure (CHF) despite multiple drug therapies. D-Ribose has been shown in animal models to improve cardiac energy metabolism and function following ischaemia. This was a prospective, double blind, randomized, crossover design study, to assess the effect of oral D-ribose supplementation on cardiac hemodynamics and quality of life in 15 patients with chronic coronary artery disease and CHF. The study consisted of two treatment periods of 3 weeks, during which either oral D-ribose or placebo was administered followed by a 1-week wash out period, and then administration of the other supplement. Assessment of myocardial functional parameters by echocardiography, quality of life using the SF-36 questionnaire and functional capacity using cycle ergometer testing was performed. The administration of D-ribose resulted in an enhancement of atrial contribution to left ventricular filling (40+/-11 vs. 45+/-9%, P=0.02), a smaller left atrial dimension (54+/-20 vs. 47+/-18 ml, P=0.02) and a shortened E wave deceleration (235+/-64 vs. 196+/-42, P=0.002) by echocardiography. Further, D-ribose also demonstrated a significant improvement of the patient's quality of life (417+/-118 vs. 467+/-128, P< or =0.01). In comparison, placebo did not result in any significant echocardiographic changes or in quality of life. This feasibility study in patients with coronary artery disease in CHF revealed the beneficial effects of D-ribose by improving diastolic functional parameters and enhancing quality of life.

Ruthenium red, ribose, and adenine enhance recovery of reperfused rat heart

Tan ZT. Tan ZT. Department of Physiology, Deborah Research Institute, Browns Mills, NJ 08015-2241.

BACKGROUND: Postischemic cardiac failure may be associated with inadequate storage of myocardial adenosine triphosphate (ATP). ATP precursors were administered to resuscitate the postischemic myocardium. METHODS: Hearts isolated from male Wistar adult rats were perfused with Krebs-Henseleit buffer (pH, 7.40), subjected to 30 minutes of global ischemia at 36 degrees C, followed by 30 minutes of retrograde reperfusion with the postischemic intervention of ruthenium red (1 microM), ribose (1 mM), and adenine (1 mM). Multiple analysis of variance was used to compare means between groups (eight rats in each group). RESULTS: In comparison with the nonischemic group, the postischemic nontreated group had a decrease in the maximum rate of left ventricular pressure rise (+dP/dt, P < 0.0005) and level of myocardial ATP (P < 0.0005) but an increase in level of mitochondrial Ca2+ (P < 0.005). In comparison with the nontreated group, ribose and adenine had no effect on all the above-mentioned parameters, and ruthenium red elevated maximum left ventricular +dP/dt (P < 0.05) and reduced mitochondrial Ca2+ (P < 0.05) with no change in ATP (P > 0.05). However, ruthenium red with ribose and adenine achieved a significant increase in maximum left ventricular +dP/dt (P < 0.0005), ATP levels (P < 0.005), and a decrease in levels of mitochondrial Ca2+ (P < 0.005). CONCLUSION: Acute postischemic cardiac failure may be related to Ca2+ overload in mitochondria. Ruthenium red may reduce mitochondrial Ca2+ overload. Ruthenium red, ribose, and adenine in combination may be capable of enhancing the recovery of myocardial high-energy phosphates and mechanical function in the postischemic myocardium

Supplemental conditionally essential nutrients in cardiovascular disease therapy

Kendler BS. Dept. of Biology, CMSV Campus, Manhattan College, Riverdale, NY 10471, USA. barry.kendler@mountsaintvincent.edu

Conditionally essential nutrients (CENs) are organic compounds that are ordinarily produced by the body in amounts sufficient to meet its physiological requirements. However, in disorders, such as cardiovascular disease (CVD), and in other physiologically stressful conditions, their biosynthesis may be inadequate. Under these circumstances, CENs become essential nutrients, comparable to vitamins. The CENs of primary importance in CVD, based on the quantity and quality of human clinical studies, are l-arginine, l-carnitine, propionyl-l-carnitine, and coenzyme Q10. Controlled studies of these CENs are reviewed in depth. Taurine is a CEN of secondary importance caused by a limited human database. Other putative CENs include alpha-lipoic acid, betaine, chondroitin sulfate, glutamine, and d-ribose, each of which is mentioned in passing. Collectively, CENs have demonstrated favorable clinical effects in CVDs, including chronic heart failure, myocardial infarction, angina pectoris, and in CVD risk factors, such as hypertension, hyperlipidemia, and lipoprotein(a). Limited research has pointed to possible benefits in CVD therapy accruing from supplementation with several CENs in combination. Additional controlled clinical studies of CENs in CVD are urgently needed. In view of the efficacy and safety of appropriate supplementation with CENs, it is strongly suggested that healthcare professionals become knowledgeable of these potentially important additions to the CVD therapeutic armamentarium.

Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart

Pasque MK, Spray TL, Pellom GL, Van Trigt P, Peyton RB, Currie WD, Wechsler AS.

Recovery for myocardial adenosine triphosphate (ATP) following moderate periods of ischemic is dependent upon the availability of adenosine monophosphate (AMP) and diphosphate (ADP) for rephosphorylation. Recovery of AMP and ADP levels following ischemia is, in turn, determined by the rates of salvage and de novo adenine nucleotide synthesis. Phosphoribosyl pyrophosphate (PRPP) availability is rate limiting in both salvage and de novo adenine nucleotide synthesis. Parenteral ribose infusions in rats have been documented to elevate myocardial PRPP levels with resultant enhancement of adenine nucleotide synthesis. In this study postischemic recovery of myocardial function and ATP levels in isolated, working rat hearts given ribose infusions before and after ischemia was compared with recovery in control hearts subjected to the same protocol without ribose administration. The mean percent of functional recovery in control hearts following 15 minutes of warm ischemia reached values of 56.7 +/- 4.1%, 63.5% +/- 4.3%, 65.9% +/- 4.6%, and 70.5% +/- 4.7% at 2, 5, 10, and 15 minutes of work following ischemia. Hearts perfused with ribose demonstrated improved mean percent return of function at similar intervals of postischemic work with values of 67.9% +/- 4.2%, 73.7% +/- 3.7%, 81.0% +/- 3.5% (* = p less than 0.02 versus control) *and 85.4% +/- 3.3%, *respectively. Determinations of myocardial ATP levels (mumoles/gm of dry weight) made at the end of 15 minutes of postischemic work were significantly higher (p less than 0.02) in the ribose-treated hearts (18.9 +/- 0.7) than in controls (16.3 +/- 0.6). Infusion of ribose before and after ischemia is a biochemically logical method of improving postischemic myocardial ATP and functional recovery by manipulation of adenine nucleotide synthetic pathways.

Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model

St Cyr JA, Bianco RW, Schneider JR, Mahoney JR Jr, Tveter K, Einzig S, Foker JE.

High energy phosphate levels are depressed following global ischemia and require several days to completely recover. Short-term methods to enhance ATP recovery have included infusion of ATP precursors, inhibition of enzymes that catabolize AMP, and membrane transport stabilization. Several precursors have been used to augment adenine nucleotide synthesis including adenosine, inosine, adenine, and ribose. Because of the short-term nature of previous experiments, recovery had been incomplete and the effects in the intact animal unknown. The purpose of this study was to determine the effects of ribose infusion in a long-term model of global ischemia and attempt to identify the precursor which limits myocardial ATP regeneration in the intact animal. Global myocardial ischemia (20 min, 37 degrees C) was produced in dogs on cardiopulmonary bypass. With reperfusion either ribose (80 mM) in normal saline or normal saline alone was infused at 1 ml/min into the right atrium and the animals were followed for 24 hr. Ventricular biopsies were obtained through an indwelling ventricular cannula prior to ischemia, at the end of ischemia, and 4 and 24 hr postischemia and analyzed for adenine nucleotides and creatine phosphate levels. Radiolabeled microspheres were used to measure myocardial and renal blood flows and no significant difference was found between ribose-treated control groups. In both groups, myocardial ATP levels fell by at least 50% at the end of ischemia. No significant ATP recovery occurred after 24 hr in the control dogs, but in the ribose-treated animals, ATP levels rebounded to 85% of control by 24 hr

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