Advertisement

Effects of intravenous verapamil on left ventricular relaxation and filling in stable angina pectoris

  • Sandro Betocchi
    Correspondence
    Address for reprints: Sandro Betocchi, MD, Cardiologia, 2a Facolta' di Medicina, Via S. Pansini, 5, I-80131 Naples, Italy.
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Federico Piscione
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Pasquale Perrone-Filardi
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Leonardo Pace
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Maurizio Cappelli-Bigazzi
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Bruno Alfano
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Andrea Ciarmiello
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Marco Salvatore
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Mario Condorelli
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
  • Massimo Chiariello
    Affiliations
    From the Institute of Internal Medicine, Cardiology, and Cardiac Surgery—Department of Cardiology, Naples, Italy

    From the Institute of Radiology-Section of Nuclear Medicine, “Federico II” University of Naples Second School of Medicine Naples, Italy

    From the Department of Nuclear Medicine, National Cancer Institute, Naples, Italy
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right-and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 ± 22 to 117 ± 16 mm Hg, p < 0.01) and the end-systolic pressure/volume ratio (2.4 ± 1.3 to 1.6 ± 0.5 mm Hg/ml, p < 0.05), and increased LV end-diastolic (13 ± 4 to 16 ± 4 mm Hg, p < 0.02) and pulmonary capillary pressures (10 ± 5 to 12 ±5 mm Hg, p < 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 ± 0.7 to 3.9 ± 0.6 liters/min/m2, p < 0.02). The time constant of isovolumic relaxation shortened (63 ± 14 to 47 ± 9 ms, p < 0.02); peak filling rate increased (370 ± 155 to 519 ± 184 ml/s, p < 0.001; 2.6 ± 1.1 to 3.3 ± 0.9 end-diastolic counts/s, p < 0.02; and 4.1 ± 1.6 to 5.5 ±1.5 stroke counts/s, p < 0.001). Percentage changes in peak filling rate were related to percentage changes in the time constant of isovolumic relaxation, the pressure asymptote, pulmonary capillary pressure, end-diastolic volume, and an index of LV diastolic asynchrony (r = 0.930, R2 = 0.864, F = 7.636, p = 0.014). Late diastolic filling was not affected by verapamil. Thus, intravenous verapamil administration in patients with CAD improved LV isovolumic relaxation and early filling. These effects are likely the consequence of both the drug's direct action on myocardium and changes in the loading conditions.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dwyer EM
        Left ventricular pressure-volume alterations and regional disorders of contraction during myocardial ischemia induced by atrial pacing.
        Circulation. 1970; 42: 1111-1122
        • Carroll JD
        • Hess OM
        • Hirzel HD
        • Krayenbuehl HP
        Exercise-induced ischemia: the influence of altered relaxation on early diastolic pressure.
        Circulation. 1983; 67: 521-528
        • Sharma B
        • Behrens TW
        • Erlein D
        • Hodges M
        • Asinger RW
        • Francis GS
        Left ventricular diastolic properties and filling characteristics during spontaneous angina pectoris at rest.
        Am J Cardiol. 1983; 52: 704-709
        • Gewirtz H
        • Ohley W
        • Walsh J
        • Shearer D
        • Sullivan MJ
        • Most AS
        Ischemia-induced impairment of left ventricular relaxation: relation to reduced diastolic filling rates of the left ventricle.
        Am Heart J. 1983; 105: 72-80
        • Bonow RO
        • Bacharach SL
        • Green MV
        • Kent KM
        • Rosing DR
        • Lipson LC
        • Leon MB
        • Epstein SE
        Impaired left ventricular diastolic filling in patients with coronary artery disease. Assessment with radionuclide angiography.
        Circulation. 1981; 64: 315-323
        • Sasayama S
        • Nonogi H
        • Miyazaki S
        • Sakurai T
        • Kawai C
        • Eiho S
        • Kuwahara M
        Changes in diastolic properties of the regional myocardium during pacing-induced ischemia in human subjects.
        J Am Coll Cardiol. 1985; 5: 599-606
        • Polak JF
        • Kemper AJ
        • Bianco JA
        • Parisi AF
        • Tow DE
        Resting early peak diastolic filling rate; a sensitive index of myocardial dysfunction in patients with coronary artery disease.
        J Nucl Med. 1982; 23: 471-478
        • Mancini GBJ
        • Slutsky RA
        • Norris SL
        • Bhargava V
        • Ashburn WL
        • Higgins CB
        Radionuclide analysis of peak filling rate, filling fraction, and time to peak filling rate. Response to supine bicycle exercise in normal subjects and patients with coronary disease.
        Am J Cardiol. 1983; 51: 43-51
        • Perrone-Filardi P
        • Betocchi S
        • Giustino G
        • Piscione F
        • Indolfi C
        • Salvatore M
        • Chiariello M
        Influence of left ventricular asynchrony on filling in coronary artery disease.
        Am J Cardiol. 1988; 62: 523-527
        • Dougherty AH
        • Naccarelli GV
        • Gray EL
        • Hicks C
        • Goldstein RA
        Congestive heart failure with normal systolic function.
        Am J Cardiol. 1984; 54: 778-782
        • Soufer R
        • Wohlgelernter D
        • Vita NA
        • Amuchestegui M
        • Sostman D
        • Berger HJ
        • Zaret BL
        Intact systolic left ventricular function in clinical congestive heart failure.
        Am J Cardiol. 1985; 55: 1032-1037
        • Bonow RO
        • Rosing DR
        • Bacharach SL
        • Green MV
        • Kent KM
        • Lipson LC
        • Maron BJ
        • Epstein SE
        Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy.
        Circulation. 1981; 64: 787-796
        • Hess OM
        • Murakami T
        • Krayenbuehl HP
        Does verapamil improve left ventricular relaxation in patients with myocardial hypertrophy?.
        Circulation. 1986; 74: 530-543
        • Betocchi S
        • Cuocolo A
        • Pace L
        • Chiariello M
        • Trimarco B
        • Alfano B
        • Ricciardelli B
        • Salvatore M
        • Condorelli M
        Effects of intravenous verapamil administration on left ventricular diastolic function in systemic hypertension.
        Am J Cardiol. 1987; 59: 624-629
        • Brush JE
        • Udelson JE
        • Bacharach SL
        • Cannon III, RO
        • Leon MB
        • Rumble TF
        • Bonow RO
        Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension.
        J Am Coll Cardiol. 1989; 14: 515-522
        • Bonow RO
        • Leon MB
        • Rosing DR
        • Kent KM
        • Lipson LC
        • Bacharach SL
        • Green MV
        • Epstein SE
        Effects of verapamil and propranolol on left ventricular systolic function and diastolic filling in patients with coronary artery disease: radionuclide angiography studies at rest and during exercise.
        Circulation. 1981; 65: 1337-1350
        • Myreng Y
        • Myhre E
        Effects of verapamil on left ventricular relaxation and filling dynamics in coronary artery disease. A study by pulsed Doppler echocardiography.
        Am Heart J. 1989; 117: 870-875
        • Mirsky I
        Assessment of diastolic function: suggested methods and future considerations.
        Circulation. 1984; 69: 836-841
        • Dodge JW
        • Kliman F
        Angiographic and radiographic determination of ventricular volume, wall thickness, and wall motion.
        Circulation. 1980; 62: 1136-1142
        • Afifi AA
        • Clark V
        Computer aided multivariate analysis.
        in: Lifetime Learning Publications, Belmont, California1984: 140-152
        • Urquhart J
        • Patterson RE
        • Bacharach SL
        • Green MV
        • Speir EH
        • Aamodt R
        • Epstein SE
        Comparative effects of verapamil, diltiazem, and nifedipine on hemodynamics and left ventricular function during acute myocardial ischemia in dogs.
        Circulation. 1984; 69: 382-390
        • Little WC
        • Cheng CP
        • Peterson T
        • Vinten-Johansen J
        Response of the left ventricular end-systolic pressure-volume relation in conscious dogs to a wide range of contractile states.
        Circulation. 1988; 78: 736-745
        • Eichhorn P
        • Grimm J
        • Koch R
        • Hess O
        • Carrol J
        • Krayenbuehl HP
        Left ventricular relaxation in patients with left ventricular hypertrophy secondary to aortic valve disease.
        Circulation. 1982; 65: 1395-1404
        • Lorell BH
        • Barry WH
        Effects of verapamil on contraction and relaxation of cultured chick embryo ventricular cells during calcium overload.
        J Am Coll Cardiol. 1984; 2: 341-348
        • Henry PD
        • Shuchleib R
        • Davis J
        • Weiss ES
        • Sobel BE
        Myocardial contracture and accumulation of mitochondrial calcium in ischemic rabbit heart.
        Am J Physiol. 1977; 232: H677-H684
        • Dilsizian V
        • Bonow RO
        • Cannon III, RO
        • Tracy CM
        • Vitale DF
        • McIntosh CL
        • Clark RE
        • Bacharach SL
        • Green MV
        The effect of coronary artery bypass grafting on left ventricular systolic function at rest: evidence for preoperative subclinical ischemia.
        Am J Cardiol. 1988; 61: 1248-1254
        • Gaasch WH
        • Blaunstein AS
        • Andrias CW
        • Donahue RP
        • Avitall B
        Myocardial relaxation. II. Hemodynamic determinants of rate of left ventricular isovolumic pressure decline.
        Am J Physiol. 1980; 239: H1-H61
        • Ishida Y
        • Meisner JS
        • Tsujoka K
        • Gallo JI
        • Yoran C
        • Frater RWM
        • Yellin EL
        Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure.
        Circulation. 1986; 74: 187-196
        • Walsh RA
        • O'Rourke RA
        Direct and indirect effects of calcium entry blocking agents on isovolumic left ventricular relaxation in conscious dogs.
        J Clin Invest. 1985; 75: 1426-1434