X-Message-Number: 13698
Date: Wed, 10 May 2000 08:16:52 -0700 (PDT)
From: Doug Skrecky <>
Subject: inosine, a cardiotonic agent

  Aviado DM.
  Inosine : a naturally occurring cardiotonic
  agent. [Review] [94 refs]
  Journal de Pharmacologie.  14 Suppl 3:47-71, 1983.
  For many years, Inosine was considered to be a simple
  metabolite of adenosine which was devoid of any cardiovascular effects. This
  theoretical ineffectiveness can be explained in the light of recent studies
  by the use of inadequate doses. In fact, higher doses of
  inosine, a non-toxic nucleoside, have demonstrated,
  experimentally, a cardiovascular activity and the pharmacological profile of
  this naturally occurring substance has been defined. Like
  adenosine, inosine is a potent coronary vasodilator. The
  vasodilatation induced by inosine is only partly due to
  increased metabolic demands. Inosine has a direct action on
  coronary artery relaxation independent of the inotropic effect. It alters the
  balance between oxygen supply and demand which is reflected by an
  intramyocardial redistribution of oxygen in favour of the sub-endocardial
  zones. Inosine acts on the coronary circulation like a
  "regulator of myocardial nutrition", unlike adenosine, which can be thought
  of as a "coronary vasoregulator". This dissociation between the two
  nucleosides is apparently due to different vascular sites of action. The
  positive inotropic action of inosine, which has been
  demonstrated in both healthy and pathological myocardium in all of the
  experimental animal species studied, is not due to stimulation of the cardiac
  beta-adrenergic receptors, as beta-blockers do not antagonize the positive
  inotropic effect of inosine. This increase in myocardial
  contractile dynamics is evident in infarcted as well as healthy areas of
  myocardium. The inotropic and coronary vasodilator effects of
  inosine are not associated with any modification of the
  chronotropic function. Inosine is not arrhythmogenic, even
  at high doses. Furthermore, it does not affect atrioventricular conduction.
  It has been demonstrated that inosine is capable of
  antagonizing ouabain induced arrhythmias. Various clinical studies confirm
  the positive inotropic action of inosine, without any
  alteration in the post-load, the pre-load or the heart rate. The positive
  inotropic action of inosine can therefore be considered to
  be selective. Together with these haemodynamic effects, it has been shown
  that the addition of inosine to cardioplegic solutions
  improves the functional recovery of the myocardium, by increasing the
  quantity of energy-rich phosphates. Similar beneficial results have been
  obtained in renal transplantation, both experimentally and in clinical
  studies. The mechanism of action of inosine remains unknown.
  Are the haemodynamic effects of this compound due to its metabolic effects?
  Are there specific myocardial purinergic receptors? (ABSTRACT TRUNCATED AT
  400 WORDS) [References: 94]

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=13698