Skip to main content
Log in

Systolic time intervals in clinical pharmacology

  • Special Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Conclusion

Heart rate-corrected STI integrate and reflect changes in ventricular inotropy, preload and afterload. STI represent a global method for the evaluation of cardiovascular performance, provided very well controlled study designs, including positive and negative controls and strictly standardised conditions are followed. STI are accurate, economic, reproducable and are very sensitive. They represent a useful non-invasive tool in clinical pharmacology for assessing the influence of drugs, their dose-effect relationships, and the time course of their effects on the cardiovascular system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ahmed SS, Levinson GE, Schwartz CJ, Ettinger PO (1972) Systolic time intervals as measures of the contractile state of the left ventricular myocardium in man. Circulation 46: 559–571

    Google Scholar 

  • Alken RG, Belz GG (1984) A comparative dose-effect study with cardiac glycosides assessing cardiac and extracardiac responses in normal subjects. J Cardiovasc Pharmacol 6: 634–640

    Google Scholar 

  • Belz GG (1981) Die systolischen Zeitintervalle als Meßmethode zur Pharmakodynamik der Herzglykoside. In: Systolische Zeitintervalle unter besonderer Berücksichtigung des Anspannungsindex. Kolloquien der Klinik für Innere Medizin der Universität Rostock, p 69–77

  • Belz GG, Aust PE, Belz G (1981a) Double blind study on the hemodynamic effects of amezinium metilsulfate in patients with orthostatic circulatory disorders. Z Kardiol 70: 706–712

    Google Scholar 

  • Belz GG, Aust PE, Doering W, Heinz M, Schneider B (1982) Pharmacodynamics of a single dose of quinidine during chronic digoxin treatment. Eur J Clin Pharmacol 22: 117–122

    Google Scholar 

  • Belz GG, Aust PE, Schneider B (1981b) Time course of the effects of single intravenous doses of digitoxin and digoxin in normal volunteers. J Cardiovasc Pharmacol 3: 1116–1125

    Google Scholar 

  • Belz GG, Bliesath H, Essig J, Neumann N, Zech K, Wurst W (1992) Differential effects of two dihydropyridine calcium antagonists in humans. Clin Pharmacol Ther 52: 68–79

    Google Scholar 

  • Belz GG, Butzer R, Erbel R, de Mey C, Nixdorf U, Schroeter V (1992) Relative sensitivity of various noninvasive estimates of the effects of isoprenaline in man. Clin Pharmacol Therap 51: 172

    Google Scholar 

  • Belz GG, Czermak E, Belz G (1979) Die zeitliche Kinetik der Wirkung von Digitoxin und β-Acetyl-Digoxin nach oraler Applikation beim Menschen. Z Kardiol 68: 77–81

    Google Scholar 

  • Belz GG, Erbel R, Schumann K, Gilfrich HJ (1978) Dose-response relationships and plasma concentrations of digitalis glycosides in man. Eur J Clin Pharmacol 13: 103–111

    Google Scholar 

  • Belz GG, Matthews JH, Beck A, Wagner G, Schneider B (1985a) Hemodynamic effects of nicorandil, isosorbide dinitrate, and dihydralazine in healthy volunteers. J Cardiovasc Pharmacol 7: 1107–1112

    Google Scholar 

  • Belz GG, Matthews JH, Graf D, Stern HC, Bachmann R, Belz G, Steinigans VW, Palm D (1985b) Dynamic responses to intravenous urapidil and dihydralazine in normal subjects. Clin Pharmacol Ther 37: 48–54

    Google Scholar 

  • Belz GG, Meinicke T, Schäfer-Korting M (1988) The relationship between pharmacokinetics and pharmacodynamics of enoximone in healthy man. Eur J Clin Pharmacol 35: 631–635

    Google Scholar 

  • Belz GG, Nübling H, Zimmer A (1976) Investigation of the pharmacodynamics and pharmacokinetics of 2-(2,4 dimethoxyphenyl)-imidazo-(4,5-b) pyridine hydrochloride (AR-L 57 CL) in man. Eur J Clin Pharmacol 10: 319–324

    Google Scholar 

  • Belz GG, Riedlinger G (1980) Nichtinvasive Untersuchungen zur kardialen Wirkung niedriger Digitoxin-Erhaltungsdosen. Z Kardiol 69: 296–306

    Google Scholar 

  • Belz GG, Spodick DH (1987) Influence of profuse sweating on systolic time intervals. Br Heart J 57: 593

    Google Scholar 

  • Belz GG, Stern HC, Butzer R (1985) Dose-response following single administrations of a new cardiac performance enhancer RO 13-6438 in normal volunteers. J Cardiovasc Pharmacol 7: 86–90

    Google Scholar 

  • Bischoff KO, Müsch M, Bucher P, Graben N, Hager W (1987) Die systolischen Zeitintervalle (STI) und ihre Abhängigkeit von der Herzfrequenz. Herz/Kreisl 19: 149–155

    Google Scholar 

  • Blumberger K (1940) Die Anspannungszeit und Austreibungszeit beim Menschen. Arch Kreislaufforschg 6: 203–292

    Google Scholar 

  • Blumberger K (1942) Die Untersuchung der Dynamik des Herzens beim Menschen. Ihre Anwendung als Herzleistungsprüfung. Ergebn Med Kinderheilk 62: 424–529

    Google Scholar 

  • Breithardt G, Jochum E, Kuhn H, Seipel L (1978) Die Wirkung verschiedener Antiarrhythmika auf die systolischen Zeitintervalle bei Normalpersonen. Z Kardiol 67: 680–687

    Google Scholar 

  • Buch CA, Lewis RD, Leighton RF, Fontana ME, Weissler AM (1970) Verification of systolic time intervals and the true isovolumic contraction time from apexcardiogram by micromanometer catheterization of the left ventricle and aorta. Circulation 42 [Suppl III]: 121

    Google Scholar 

  • Buch J, Egeblad H, Hansen PB, Kjaergard H, Waldorff S, Steiness E (1980) Correlation between changes in systolic time intervals and left ventricular end — diastolic diameter after preload reduction. Br Heart J 44: 668–671

    Google Scholar 

  • Cardioli E, Mantovani BA, D'Elia N, Martinelli M (1977) Behaviour of myocardiol contractility during the course of an acute infarction. Drug Res 27: 1493–1498

    Google Scholar 

  • Cardus D, Vera L (1974) Systolic time intervals at rest and during exercise. Cardiol 59: 133–153

    Google Scholar 

  • Carliner NH, Gilbert CA, Pruitt AW, Goldberg LI (1974) Effects of maintenance digoxin therapy on systolic time intervals and serum digoxin concentrations. Circulation 50: 94–98

    Google Scholar 

  • Chirife R, Spodick DH (1972) Densitography: a new method for evaluation of cardiac performance at rest and during exercise. Am Heart J 83: 493–503

    Google Scholar 

  • Erbel R, Belz GG (1977) Untersuchungen zur Meßmethode der systolischen Zeitintervalle. Z Kardiol 66: 433–435

    Google Scholar 

  • Essig J (1988) Entwicklung und Anwendung einer neuen klinisch-pharmakologischen Methode zur Analyse der Dynamik, Effektkinetik und pharmakodynamischen Potenz von Angiotensin Konversions Enzym (ACE)-Hemmstoffen mittels Erstellung systemischer Angiotensin I-Dosiswirkungskurven am Menschen. Inauguraldissertation, Universität Mainz, pp 57–61

    Google Scholar 

  • Fieldman A, Beebe RD, Chow MSS (1977) The effect of quinidine sulfate on QRS duration and QT and systolic time intervals in man. J Clin Pharmacol 17: 134–139

    Google Scholar 

  • Forester W, Lewis RP, Weissler AM, Wilke TA (1974) The onset and magnitude of the contractile response to commonly used digitalis glycosides in normal subjects. Circulation 49: 517–521

    Google Scholar 

  • Follath F, Kersting F, Lewis GRJ, Walden RJ, Woolhouse NM, Dollery CT (1976) Cardiovascular effects of a new inotropic drug in dog and normal man. Clin Pharmacol and Therap 20: 24–30

    Google Scholar 

  • Gibson DG (1978) Use of the systolic time intervals in clinical pharmacology. Brit J Clin Pharmacol 6: 97–102

    Google Scholar 

  • Gillilan RE, Parnes WP, Khan MA, Bouchard RJ, Warbasse JR (1979) The prognostic value of systolic time intervals in angina pectoris patients. Circulation 60: 268–274

    Google Scholar 

  • Griebenow R, Meier CH, Saborowski F (1981) Vergleichende Bestimmung der systolischen Zeitintervalle. Z Kardiol 70: 687–692

    Google Scholar 

  • Halabi A, Linde M, Saathoff H, Nakhodian A, Dylewicz P, Kirch W (1990) Hemodynamic effects of diltiazem and nitrendipine assessed by noninvasive methods in patients with congestive heart failure. Am J Noninvas Cardiol 4: 60–64

    Google Scholar 

  • Harris WS, Aytan N, Pouget JM (1973) Effects of nitroglycerin on responses of the systolic time intervals to exercise. Circulation 47: 499–507

    Google Scholar 

  • Harris WS, Schoenfeld CD, Weissler AM (1967) Effects of adrenergic receptor activation and blockade on the systolic preejection period, heart rate, and arterial pressure in man. J Clin Invest 46: 1704–1714

    Google Scholar 

  • Hassan S, Turner P (1983) Systolic time intervals: a review of the method in the non-invasive investigation of cardiac function in health, disease and clinical pharmacology. Postgrad Med J 59: 423–434

    Google Scholar 

  • Hoffmann A, Sefidpar M, Burckhardt D (1974) Systolische Zeitintervalle in Ruhe und unter Belastung bei unterschiedlichem Schweregrad von Linksherzinsuffizienz. Z Kardiol 63: 768–777

    Google Scholar 

  • Imhof PR, Müller Ph, Keller R (1987) Pharmacological profiling of cardiovascular agents in healthy volunteers by means of non-invasive methods. Meth Find Exptl Clin Pharmacol 9: 829–832

    Google Scholar 

  • Ishikawa M, Ishikawa K (1986) Influence of profuse sweating on systolic time intervals. Brit Heart J 56: 176–178

    Google Scholar 

  • Johnson BF, Meeran MK, Frank A, Taylor SH (1981) Systolic time intervals in measurement of inotropic response to drugs. Br Heart J 46: 513–521

    Google Scholar 

  • Joubert P, Belz GG (1987) Are pre-ejection period changes specific for inotropic effects? Eur J Clin Pharmacol 33: 335–336

    Google Scholar 

  • Katz LN, Feil HS (1923) Clinical observations on the dynamics of ventricular systole. Arch Int Med 32: 672–692

    Google Scholar 

  • Kelman AW, Sumner DJ, Whiting B (1981) The prediction of individual systolic time interval v heart rate regression equations. Br J Clin Pharmacol 12: 21–30

    Google Scholar 

  • Khan AH, Spodick DH (1972) The first derivative of the carotid displacement pulse. Am Heart J 84: 470–477

    Google Scholar 

  • Lance VQ, Spodick DH (1975) Constand-load versus heart rate-targeted exercise: responses of systolic intervals. J Appl Physiol 38: 794–800

    Google Scholar 

  • Van Leeuwen P (1988) Die Bedeutung der Herz-Zeitintervalle zur Erfassung der Herzfunktion unter besonderer Berücksichtigung der Frequenzabhängigkeit. Inauguraldissertation, Universität Witten/ Herdecke, pp 41–45

    Google Scholar 

  • Van Leeuwen P, Kuemmell HC (1987) Respiratory modulation of cardiac time intervals. Br Heart J 58: 129–135

    Google Scholar 

  • Levi GF, Ratti S, Cardone G, Basagni M (1982) On the reliability of systolic time intervals. Cardiol 69: 157–165

    Google Scholar 

  • Lewis RP, Boudoulas H, Welch TG, Forester WF (1976) Usefulness of systolic time intervals in coronary artery disease. Am J Cardiol 37: 787–796

    Google Scholar 

  • Lewis RP, Leighton RF, Forester WF, Weissler AM (1974) Systolic time intervals. In: Weissler AM (ed) Noninvasive Cardiology. Grune & Statton 301–368

  • Lewis RP, Rittgers SE, Forester WF, Boudoulas H (1977) A critical review of the systolic time intervals. Circulation 56: 146–158

    Google Scholar 

  • Maass H, Weber A (1952) Herzschallregistrierung mittels differenzierender Filter. Cardiologia 21: 773–794

    Google Scholar 

  • Mäntysaari M, Länsimes E (1992) Heart rate correction based on “universal” regression equation — erroneous conclusions when studying cardiac mechanical function during stress. Europ Heart J 13: 1088–1091

    Google Scholar 

  • McDonald IG, Hobson ER (1974) A comparison of the relative value of noninvasive techniques — echocardiography, systolic time intervals, and apexcardiography — in the diagnosis of primary myocardial disease. Am Heart J 88: 454–462

    Google Scholar 

  • Mertens HM, Mannebach H, Trieb G, Gleichmann U (1981) Influence of heart rate on systolic time intervals: effects of atrial pacing versus dynamic exercise. Clin Cardiol 4: 22–37

    Google Scholar 

  • Metzger CC, Chough CB, Kroetz FW, Leonard JJ (1970) True isovolumic contraction time, its correlation with two external indexes of ventricular performance. Am J Cardiol 25: 434–441

    Google Scholar 

  • De Mey C, Belz GG, Nixdorf U, Butzer R, Schroeter V, Meyer J, Erbel R (1992) Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoprenaline in healthy volunteers. Clin Pharmacol Ther 52: 609–619

    Google Scholar 

  • De Mey C, Enterling D (1986) Assessment of the hemodynamic response to single passive head up tilt by non-invasive methods in normotensive subjects. Meth Find Clin Pharmacol 8: 449–457

    Google Scholar 

  • De Mey C, Enterling D, Hanft G (1991) Noninvasive assessment of the inodilator action of amrinone in healthy man. Eur J Clin Pharmacol 40: 373–378

    Google Scholar 

  • De Mey C, Hansen-Schmidt S, Enterling D (1987) Food intake as a source of methodological bias in cardiovascular clinical pharmacology. Pharmaceut Med 2: 251–257

    Google Scholar 

  • Nakamura Y, Wiegner AW, Gaasch WH, Bing OHL (1983) Systolic time intervals: assessment by isolated cardiac muscle studies. J Amer Coll Cardiol 2: 973–978

    Google Scholar 

  • Roland EQ, Safar ME, Lelguen ClE, Aboras NE, Weis YA, Milliez PM (1977) Effect of certain antiadrenergic agents on systolic time intervals in essential hypertension. Eur J Clin Pharmacol 11: 423–427

    Google Scholar 

  • Rousson D, Galleyrand J, Silie M, Boissel JP (1987) Uncorrected pre-ejection period: a simple noninvasive measurement for pharmacodynamic screening of inotropic activity. Eur J Clin Pharmacol 31: 559–562

    Google Scholar 

  • Schäfer-Korting M, Belz GG, Brauer J, Alken RG, Mutschler E (1987) Digoxin concentrations in serum and cantharides blister fluid: Correlations with cardiac response. Clin Pharmacol Ther 42: 613–620

    Google Scholar 

  • Scott MJ, Randolph PH, Leier CV (1989) Reproducibility of systolic and diastolic time intervals in normal humans: an important issue in clinical cardiovascular pharmacology. J Cardiovasc Pharmacol 13: 125–130

    Google Scholar 

  • Spodick DH, Ball HG, Pigott VM (1978) Effects of recording speeds on precision of time-based polycardiographic measurements. Br Heart J 40: 1344–1348

    Google Scholar 

  • Spodick DH, Doi YL, Bishop RL, Hashimoto T (1984) Systolic time intervals reconsidered. Reevaluation of the preejection period: absence of relation to heart rate. Am J Cardiol 53: 1667–1670

    Google Scholar 

  • Spodick DH, Kumar S (1968) Left ventricular ejection period. Am Heart J 76: 70–73

    Google Scholar 

  • Spodick DH, Meyer M, St Pierre JR (1971) Effect of upright tilt on the phases of the cardiac cycle in normal subjects. Cardiovasc Res 5: 210–214

    Google Scholar 

  • Stack RS, Lee CC, Reddy BP, Taylor ML, Weissler AM (1976) Left ventricular performance in coronary artery disease evaluated with systolic time intervals and echocardiography. Am J Cardiol 37: 331–339

    Google Scholar 

  • Staffeld HF, Mertens HM, Gleichmann U (1978) Der Einfluß von dynamischer Belastung und körperlichem Training auf die systolischen Zeitintervalle bei Gesunden und Patienten mit koronarer Herzkrankheit. Z Kardiol 67: 305–316

    Google Scholar 

  • Stafford R, Harris WS, Weissler AM (1970) Left ventricular systolic time intervals as indices of postural circulatory tress in man. Circulation 41: 485–492

    Google Scholar 

  • Stern H, Konetschny I, Herrmann L, Säwe U, Belz GG (1985a) Cardiovascular effects of single doses of the antidepressants amitriptyline and lofepramine in healthy subjects. Pharmacopsychiat 78: 272–277

    Google Scholar 

  • Stern HC, Matthews JH, Belz GG (1986) Intrinsic and reflex actions of verapamil and nifedipine: assessment in normal subjects by noninvasive techniques and autonomic blockade. Eur J Clin Pharmacol 29: 541–547

    Google Scholar 

  • Stern HC, Matthews JH, Belz GG (1984) Influence of dihydralazine induced afterload reduction on systolic time intervals and echocardiography in healthy subjects. Br Heart J 52: 435–439

    Google Scholar 

  • Stern HC, Wolf GK, Belz GG (1985b) Comparative measurements of left ventricular ejection time by mechano-, echo- and electrical impedance cardiography. Drug Res 35: 1582–1586

    Google Scholar 

  • Warrington SJ (1985) Systolic time intervals — A new technique in clinical pharmacology. Meth Find Exp Clin Pharmacol 7: 93–98

    Google Scholar 

  • Weissler AM (1983) Interpreting systolic time intervals in man. J Amer Coll Cardiol 2: 1019–1020

    Google Scholar 

  • Weissler AM, Garrard CL (1972) Systolic time intervals in cardiac disease. Mod Conc Cardiovasc Dis 40: 1–8

    Google Scholar 

  • Weissler AM, Harris LC, White GD (1963) Left ventricular ejection time index in man. J Appl Physiol 18: 919–923

    Google Scholar 

  • Weissler AM, Harris WS, Schoenfeld CD (1968) Systolic time intervals in heart failure in man. Circulation 37: 149–159

    Google Scholar 

  • Weissler AM, Harris WS, Schoenfeld CD (1969) Beside technics for the evaluation of ventricular function in man. Am J Cardiol 23: 577–583

    Google Scholar 

  • Weissler AM, O'Neill WW, Sohn YH, Stack RS, Chew PC, Reed AH (1981) Prognostic significance of sytolic time intervals after recovery from myocardial infarction. Am J Cardiol 48: 995–1001

    Google Scholar 

  • Weissler AM, Peeler RG, Roehll WH (1961) Relationships between left ventricular ejection time, stroke volume, and heart rate in normal individuals and patients with cardiovascular disease. Am Heart J 62: 367–379

    Google Scholar 

  • Weissler AM, Snyder JR, Schoenfeld CD (1966) Assay of digitalis glycosides in man. Amer J Cardiol 17: 768–780

    Google Scholar 

  • Weissler AM, Schoenfeld CD (1970) Effect of digitalis on systolic time intervals in heart failure. Am J Med Sci 259: 4–20

    Google Scholar 

  • Willems J, Kesteloot H (1967) The left ventricular ejection time. Its relation to heart rate, mechanical systole and some anthropometric data. Ext Act Cardiol 22: 401–425

    Google Scholar 

  • Willems JL, Kyle MC, Pillsburg HC, Freis ED (1975) First derivative of the apex cardiogram and systolic time intervals in evaluation of myocardial contractility in man. Am J Cardiol 36: 873–879

    Google Scholar 

  • Wolf GK, Belz GG (1981) Methods of frequency — correction for systolic time intervals. Basic Res Cardiol 76: 182–188

    Google Scholar 

  • Wolf GK, Belz GG, Stauch M (1978) Systolic time intervals — correction for heart rate. Basic Res Cardiol 73: 85–96

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Q., Belz, G.G. Systolic time intervals in clinical pharmacology. Eur J Clin Pharmacol 44, 415–421 (1993). https://doi.org/10.1007/BF00315536

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00315536

Key words

Navigation