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Heart Failure |

Flosequinan, a new vasodilator: Systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure FREE

Patricia G. Cavero, MD; Teresa De Marco, MD; Michael Kwasman, MD; Debra Lau, RN; Maggie Lau, RN; Kanu Chatterjee, MB, FRCP, FACC
[+] Author Information

This work was supported in part by grants from the Boots Company (USA). Shreveport, Louisiana.Address for correspondence: Kanu Chatterjee, MB, FRCP, University of California, Moffitt Hospital, Room 1186, Box 0124, San Francisco, California 94143.

J Am Coll Cardiol. 1992;20(7):1542-1548. doi:10.1016/0735-1097(92)90448-V
Published online

  Objectives. The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure.Background. Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure.Methods. Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment.Results. The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow.Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics.Conclusions. Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system.

References

Adler  R, Chatterjee  K, Ports  T, Brundage  B, Hiramatsu  B, Parmley  W; Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation. 61 1980:931-937.
CrossRef | PubMed
Massie  BM, Ports  T, Chatterjee  K; Long term sodilator therapy for heart failure: clinical response and its relationship to hemodynamic measurement and ventricular ectopic activity. Circulation. 63 1981:269-278.
CrossRef | PubMed
Kessler  PD, Packer  M, Medina  N, Yushak  M; Cumulative hemodynamic response to short-term treatment with Flosequinan (BTS 49465), a new direct-acting vasodilator drug, in severe chronic congestive heart failure. J Cardiovasc Pharmacol. 12 1988:6-11.
CrossRef | PubMed
Cowley  AJ, Wynne  RD, Stainer  K, Fullwood  L, Rowley  JM, Hampton  JR; Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects. BMJ. 297 (6642) 1988:169-173.
CrossRef | PubMed
Cowley  AJ, Wynne  RD, Hampton  JP; The effects of BTS 49465 on blood pressure and peripheral arteriolar and venous tone in normal volunteers. J Hypertension. 2 (suppl 3) 1984:547-549.
CrossRef
Allcock  AA, Frodsham  G, Sim  MF; Effects of Flosequinan, a novel arteriovenous dilating agent on cGMP levels in rat isolated aortic strips (abstr). Br J Pharmacol. 94 1988:430P
Falotico  R, Haertlein  BJ, Lakas-Weiss  CS, Salata  JJ, Tobia  AJ; Positive inotropic and hemodynamic properties of flosequinan, a new vasodilator, and a sulfone metabolite. J Cardiovasc Pharmacol. 14 1989:412-418.
CrossRef | PubMed
Corin  WJ, Monrad  ES, Strom  JA, Giustino  S, Sonnenblick  ES, LeJemtel  T; Flosequinan: a vasodilator with positive inotropic activity. Am Heart J. 121 1991:537-540.
CrossRef | PubMed
Greenberg  S, Touhey  B, Paul  J; Effect of flosequinan (BTS 49465) on myocardial oxygen consumption. Am Heart J. 119 1990:1355-1366.
CrossRef | PubMed
Francis  GS, Goldsmith  SR, Levine  TB; The neurohormonal axis in congestive heart failure. Ann Intern Med. 101 1984:370-377.
PubMed
Raine  A, Burgisser  E, Muller  F, Bolli  P, Burkart  F, Buhler  F; Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med. 315 1986:533-537.
CrossRef | PubMed
Chatterjee  K; Vasodilator therapy for heart failure.Cohn  JN; Drug Treatment of Heart Failure. Secaucus: Advanced Therapeutics Communications International. 1988:199-226.
Ganz  W, Tanura  K, Marais  HS, Donoso  R, Yoshida  S, Swan  HS; Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation. 44 1971:181-195.
CrossRef | PubMed
Pepine  CJ, Mehta  J, Webster  WW  Jr, Nedrols  WW; In vivo validation of thermodilution method to determine regional left ventricular blood flow in patients with coronary disease. Circulation. 58 1978:795-802.
CrossRef | PubMed
Mathey  DG, Chatterjee  K, Tybert  JV, Lekven  J, Brundage  B, Parmley  WW; Coronary sinus reflux: a source of error in the measurement of thermodilution coronary sinus flow. Circulation. 57 1978:778-786.
CrossRef | PubMed
Peuler  JD, Johnson  GA; Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci. 21 1977:625-636.
CrossRef | PubMed
Glantz  SA, Slinker  BK; Primer of Applied Regression And Analysis of Variance. 1990 McGraw-Hill New York:421-430.
Haas  GJ, Binkley  PF, Carpenter  JA, Leier  CV; Central and regional hemodynamic effects of flosequinan in congestive heart failure. Am J Cardiol. 63 1989:1354-1359.
CrossRef | PubMed
Wynne  RD, Crampton  EL, Hind  ID; The pharmacokinetics and haemodynamics of BTS 49465 and its major metabolite in healthy volunteers. Eur J Clin Pharmacol. 28 1985:659-664.
CrossRef | PubMed
Burnett  J, Kao  PC, Hu  DC, Heser  W, Heublein  D, Granger  JP; Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 231 1986:1145-1147.
CrossRef | PubMed
Lattion  AL, Michel  JB, Arnauld  E, Corvol  P, Soubert  F; Myocardial recruitment during ANFmRNA increases with volume overload in the rat. Am J Physiol. 251 1986:H890-H896.
PubMed
Edwards  BS, Ackermann  DM, Lee  ME, Reeder  GS, Wold  LE, Burnell  JC  Jr; Identification of atrial natriuretic factor within ventricular tissue in hamsters and humans with congestive heart failure. J Clin Invest. 81 1988:82-86.
CrossRef | PubMed

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References

Adler  R, Chatterjee  K, Ports  T, Brundage  B, Hiramatsu  B, Parmley  W; Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation. 61 1980:931-937.
CrossRef | PubMed
Massie  BM, Ports  T, Chatterjee  K; Long term sodilator therapy for heart failure: clinical response and its relationship to hemodynamic measurement and ventricular ectopic activity. Circulation. 63 1981:269-278.
CrossRef | PubMed
Kessler  PD, Packer  M, Medina  N, Yushak  M; Cumulative hemodynamic response to short-term treatment with Flosequinan (BTS 49465), a new direct-acting vasodilator drug, in severe chronic congestive heart failure. J Cardiovasc Pharmacol. 12 1988:6-11.
CrossRef | PubMed
Cowley  AJ, Wynne  RD, Stainer  K, Fullwood  L, Rowley  JM, Hampton  JR; Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects. BMJ. 297 (6642) 1988:169-173.
CrossRef | PubMed
Cowley  AJ, Wynne  RD, Hampton  JP; The effects of BTS 49465 on blood pressure and peripheral arteriolar and venous tone in normal volunteers. J Hypertension. 2 (suppl 3) 1984:547-549.
CrossRef
Allcock  AA, Frodsham  G, Sim  MF; Effects of Flosequinan, a novel arteriovenous dilating agent on cGMP levels in rat isolated aortic strips (abstr). Br J Pharmacol. 94 1988:430P
Falotico  R, Haertlein  BJ, Lakas-Weiss  CS, Salata  JJ, Tobia  AJ; Positive inotropic and hemodynamic properties of flosequinan, a new vasodilator, and a sulfone metabolite. J Cardiovasc Pharmacol. 14 1989:412-418.
CrossRef | PubMed
Corin  WJ, Monrad  ES, Strom  JA, Giustino  S, Sonnenblick  ES, LeJemtel  T; Flosequinan: a vasodilator with positive inotropic activity. Am Heart J. 121 1991:537-540.
CrossRef | PubMed
Greenberg  S, Touhey  B, Paul  J; Effect of flosequinan (BTS 49465) on myocardial oxygen consumption. Am Heart J. 119 1990:1355-1366.
CrossRef | PubMed
Francis  GS, Goldsmith  SR, Levine  TB; The neurohormonal axis in congestive heart failure. Ann Intern Med. 101 1984:370-377.
PubMed
Raine  A, Burgisser  E, Muller  F, Bolli  P, Burkart  F, Buhler  F; Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med. 315 1986:533-537.
CrossRef | PubMed
Chatterjee  K; Vasodilator therapy for heart failure.Cohn  JN; Drug Treatment of Heart Failure. Secaucus: Advanced Therapeutics Communications International. 1988:199-226.
Ganz  W, Tanura  K, Marais  HS, Donoso  R, Yoshida  S, Swan  HS; Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation. 44 1971:181-195.
CrossRef | PubMed
Pepine  CJ, Mehta  J, Webster  WW  Jr, Nedrols  WW; In vivo validation of thermodilution method to determine regional left ventricular blood flow in patients with coronary disease. Circulation. 58 1978:795-802.
CrossRef | PubMed
Mathey  DG, Chatterjee  K, Tybert  JV, Lekven  J, Brundage  B, Parmley  WW; Coronary sinus reflux: a source of error in the measurement of thermodilution coronary sinus flow. Circulation. 57 1978:778-786.
CrossRef | PubMed
Peuler  JD, Johnson  GA; Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci. 21 1977:625-636.
CrossRef | PubMed
Glantz  SA, Slinker  BK; Primer of Applied Regression And Analysis of Variance. 1990 McGraw-Hill New York:421-430.
Haas  GJ, Binkley  PF, Carpenter  JA, Leier  CV; Central and regional hemodynamic effects of flosequinan in congestive heart failure. Am J Cardiol. 63 1989:1354-1359.
CrossRef | PubMed
Wynne  RD, Crampton  EL, Hind  ID; The pharmacokinetics and haemodynamics of BTS 49465 and its major metabolite in healthy volunteers. Eur J Clin Pharmacol. 28 1985:659-664.
CrossRef | PubMed
Burnett  J, Kao  PC, Hu  DC, Heser  W, Heublein  D, Granger  JP; Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 231 1986:1145-1147.
CrossRef | PubMed
Lattion  AL, Michel  JB, Arnauld  E, Corvol  P, Soubert  F; Myocardial recruitment during ANFmRNA increases with volume overload in the rat. Am J Physiol. 251 1986:H890-H896.
PubMed
Edwards  BS, Ackermann  DM, Lee  ME, Reeder  GS, Wold  LE, Burnell  JC  Jr; Identification of atrial natriuretic factor within ventricular tissue in hamsters and humans with congestive heart failure. J Clin Invest. 81 1988:82-86.
CrossRef | PubMed

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