W J Paulus

OLV Ziekenhuis Aalst, Alost, Flanders, Belgium

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Publications (47)512.53 Total impact

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    Walter J. Paulus · Stefan Frantz · Ralph A. Kelly

    Preview · Article · Dec 2001 · Circulation
  • Walter J. Paulus
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    ABSTRACT: Nitric oxide (NO) has effects on contractility, energetics and gene expression of failing myocardium. Initial studies on isolated cardiomyocytes showed NO to reduce systolic shortening but intracoronary infusions of NO-donors or of NO synthase (NOS) inhibitors failed to elicit changes in baseline LV contractility indices such as LVdP/dtmax. Intracoronary infusions of NO-donors or of substance P, which releases NO from the coronary endothelium, however demonstrated NO to induce a downward displacement of the left ventricular (LV) diastolic pressure–volume relation, consistent with increased LV diastolic distensibility. In end-stage failing myocardium, the increased oxygen consumption is related to reduced NO production and in isolated cardiomyocytes, NO blunts the norepinephrine-induced expression of the fetal gene programme thereby preserving myocardial calcium homeostasis. In dilated cardiomyopathy, changed endomyocardial NOS gene expression has been reported. Because of lower endomyocardial NOS gene expression in patients with higher functional class and lower LV stroke work, increased endomyocardial NOS gene expression seems to be beneficial rather than detrimental for the failing heart. A beneficial effect of increased NOS gene expression could result from NO's ability to increase LV diastolic distensibility, to augment LV preload reserve, to reduce myocardial oxygen consumption and to prevent downregulation of calcium ATPase. Upregulated endomyocardial NOS gene expression has also been reported in athlete's heart and could therefore play a role in physiological LV remodeling. Reduced endomyocardial NO content because of decreased NO or increased superoxide production could lower LV diastolic distensibility and contribute to diastolic heart failure. In many conditions such as aging, hypertension, diabetes or posttransplantation, the increased incidence of diastolic heart failure is indeed paralleled by reduced endothelium-dependent vasodilation.
    No preview · Article · Apr 2001 · Heart Failure Reviews
  • W J Paulus
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    ABSTRACT: Modulation by NO of systolic myocardial function received widespread attention but most studies focused on potential negative inotropic properties of NO. The very original observations on the effects of NO on myocardial contraction already provided evidence that NO modified myocardial contractile performance mainly through a relaxation-hastening effect (i.e. earlier onset of relaxation) and through an increase in myocardial distensibility. The present review discusses the relaxation hastening and distensibility-increasing effects of NO in experimental preparations, in the normal human heart, in left ventricular hypertrophy of aortic stenosis, in the human allograft and in dilated nonischemic cardiomyopathy. This 'diastolic flip side' of the myocardial effects of NO appears to be beneficial especially for patients who are dependent on the LV Frank-Starling response to maintain cardiac output.
    No preview · Article · Jan 2001 · Heart Failure Reviews
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    Walter J. Paulus
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    ABSTRACT: In the dilated and failing heart, elevated LV end-diastolic wall stress causes myocardial expression of cytokines, which directly or indirectly influence LV contractile performance and remodeling [22]. Due to poor diffusion of cytokines into the coronary effluent, the contribution of this myocardial production to the raised plasma levels is probably limited. Raised plasma levels of cytokines in heart failure are therefore more likely the result of extramyocardial production because of altered tissue perfusion and tissue hypoxia possibly modulated by bacterial endotoxin release from the gut.
    Preview · Article · Jan 2000 · European Journal of Heart Failure
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    W J Paulus · A M Shah

    Preview · Article · Sep 1999 · Cardiovascular Research
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    ABSTRACT: Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy. In patients with dilated, nonischemic cardiomyopathy, invasive measures of LV contractile performance were derived from LV microtip pressure recordings and angiograms and correlated with intensity of gene expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simultaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial expression of NOS2 was linearly correlated with LV stroke volume (P=0.001; r=0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003; r=0.62). In patients with elevated LV end-diastolic pressure (>16 mm Hg), a closer correlation was observed between endomyocardial expression of NOS2 and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression of NOS3 was linearly correlated with LV stroke volume (P=0.01; r=0.53) and LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO) as a mediator of the observed correlations, substance P (which causes endothelial release of NO) was infused intracoronarily (n=12). In patients with elevated LV end-diastolic pressure, an intracoronary infusion of substance P increased LV stroke volume from 72+/-13 to 91+/-16 mL (P=0.06) and LV stroke work from 67+/-11 to 90+/-15 g. m (P=0.03) and shifted the LV end-diastolic pressure-volume relation to the right. In patients with dilated cardiomyopathy, an increase in endomyocardial NOS2 or NOS3 gene expression augments LV stroke volume and LV stroke work because of a NO-mediated rightward shift of the diastolic LV pressure-volume relation and a concomitant increase in LV preload reserve.
    Preview · Article · Jun 1999 · Circulation
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    M Vanderheyden · E Kersschot · W J Paulus
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    ABSTRACT: In patients with heart failure endothelium-dependent vasodilation of the forearm conduit vessels is impaired possibly because of elevated plasma levels of pro-inflammatory cytokines. The effect of elevated plasma cytokines on endothelium-dependent vasodilation of forearm conduit vessels was therefore serially investigated in 16 patients with congestive heart failure during an episode of acute failure and at the time of recompensation. Pro-inflammatory cytokine levels and hyperaemic brachial artery diameters were obtained shortly after admission for an episode of acute heart failure and 11 +/- 3 days later at the time of recompensation, which was obtained using diuretic therapy without changing other cardiovascular medications. Serum concentrations (Mean +/- SD) of tumour necrosis factor alpha (TNF-alpha) (decompensation vs recompensation: 25 +/- 23 pg.ml-1 vs 26 +/- 17 pg.ml-1) and interleukine 6 (IL-6) (decompensation vs recompensation: 27 +/- 24 pg.ml-1 vs 20 +/- 18 pg.ml-1), determined in venous blood using immunoradiometric assays were elevated but remained unaltered following recompensation. Brachial artery diameter, derived from high-resolution ultrasound scans at rest and during reactive hyperaemia, 90 s after forearm cuff deflation, increased significantly during reactive hyperaemia at the time of admission (3.4 +/- 0.7 mm vs 4.0 +/- 0.5 mm; P = 0.014) and following recompensation (3.4 +/- 0.5 mm vs 3.8 +/- 0.2 mm; P = 0.032). The brachial artery diameter during recompensation expressed as a percentage of the baseline value was similar at both intervals (decompensation vs recompensation: 117 +/- 14% vs 116 +/- 10%; P = ns). At the time of decompensation, the correlation between TNF-alpha and the percentage change in brachial artery diameter following reactive hyperaemia was absent (r = 0.098; P = 0.719). The same correlation became significant at the time of recompensation (r = 0.750; P = 0.001). In patients with congestive heart failure, plasma levels of pro-inflammatory cytokines correlate with endothelium-dependent vasodilation of the brachial artery following recompensation, but not during an acute episode of heart failure.
    Full-text · Article · Jun 1998 · European Heart Journal

  • No preview · Article · Jan 1998
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    ABSTRACT: Myocardial expression of inducible (i) nitric oxide (NO) synthase (iNOS) gene has been reported in transplant recipients and in dilated cardiomyopathy. NO derived from NO donor or from coronary endothelium has previously been shown in the human heart to reduce end-systolic left ventricular (LV) pressure, especially during beta-adrenoreceptor stimulation, because of earlier onset of LV relaxation. The present study investigated in transplant recipients whether a similar cardiodepressant effect could be attributed to NO derived from iNOS. In 16 transplant recipients who were free of rejection or graft vasculopathy, microtip LV pressure recordings, LV angiograms, and endomyocardial biopsies were obtained at annual coronary angiography. In 8 transplant recipients, microtip LV pressure recordings were obtained during intravenous dobutamine (5 microg x kg(-1) x min(-1)). Competitive reverse transcription-polymerase chain reaction of iNOS mRNA was performed on the endomyocardial biopsies, and the intensity of iNOS mRNA expression was quantified on a scale ranging from 0 to 5+. All measures of baseline LV function were comparable in transplant recipients with low (< or = 2+) or high myocardial iNOS mRNA. During intravenous dobutamine infusion, there was a significant correlation between the abbreviation of LV electromechanical systole time (LVEST is the time from onset of QRS to dP/dt(min)) and the rise of LV dP/dt(max) (r=.79; P<.02). By use of a multiple regression analysis, addition of the intensity of iNOS mRNA expression as an independent variable significantly (P<.005) improved the correlation between deltaLVEST and deltaLV dP/dt(max) (P<.001; r=.97), implying a larger abbreviation of LV contraction for a similar rise in LV dP/dt(max), when myocardial iNOS mRNA was higher. The larger abbreviation of LV contraction in-patients with high iNOS mRNA was associated with a decrease in LV end-systolic pressure (-31+/-16 mm Hg). Myocardial iNOS gene expression in the human allograft influences the LV contractile response to beta-adrenergic stimulation through earlier onset of LV relaxation and reduction of LV end-systolic pressure. These effects are similar to the LV contractile effects of NO derived from NO donor or from coronary endothelium.
    No preview · Article · Dec 1997 · Circulation
  • J Bartunek · A M Shah · M Vanderheyden · W J Paulus
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    ABSTRACT: In humans, intracoronary infusion of substance P reduces left ventricular end-systolic pressure and left ventricular peak systolic pressure because of earlier onset of left ventricular relaxation induced by paracrine myocardial action of mediators released from the coronary endothelium. The present study investigated in humans the effects of beta-adrenergic stimulation, which also induces earlier left ventricular relaxation, on the left ventricular myocardial contractile response to intracoronary infusion of substance P. Data were obtained in 13 patients after cardiac transplantation and in 3 patients with dilated nonischemic cardiomyopathy. Microtip left ventricular pressure recordings were obtained during a 5-minute intracoronary infusion of substance P (20 pmol/min) under control conditions and then repeated during concurrent intravenous administration of dobutamine. In the presence of dobutamine, intracoronary substance P caused a greater fall in left ventricular end-systolic pressure (transplantation control, -9 +/- 11 versus transplantation dobutamine, -20 +/- 18 mm Hg [P < .05]; cardiomyopathy control, -4 +/- 1 versus cardiomyopathy dobutamine, -10 +/- 3 mm Hg [P < .05]) and in left ventricular peak systolic pressure (transplantation control, -14 +/- 10 versus transplantation dobutamine, -30 +/- 22 mm Hg [P < .01]; cardiomyopathy control, -9 +/- 7 versus cardiomyopathy dobutamine, -15 +/- 6 mm Hg [P = .1]). Dobutamine enhances the cardiodepressant effect on myocardial contractile performance of receptor-mediated coronary endothelial stimulation in transplant recipients and in patients with dilated nonischemic cardiomyopathy. This enhancement could result from a potentiating interaction of the relaxation-hastening effect exerted by beta-adrenergic stimulation and by mediators released from the coronary endothelium, such as nitric oxide.
    No preview · Article · Jan 1997 · Circulation
  • P Mohan · D L Brutsaert · W J Paulus · S U Sys
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    ABSTRACT: Cardiac endothelium releases a number of factors that may modulate performance of underlying cardiac muscle. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cGMP, may be involved in this cardiac modulation. We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle. Modulation of these effects by endocardial endothelium (EE) and by cholinergic and adrenergic stimulation was also investigated. Concentration-response curves with addition of NO-releasing nitrovasodilators (SNP, SIN-1, SNAP) and 8-bromo-cGMP resulted in a biphasic inotropic response. Although administration of low concentrations induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. The response to high concentrations of 8-bromo-cGMP was shifted to the right in muscles with damaged EE, whereas cholinergic stimulation shifted the curve leftward. Zaprinast caused a monophasic concentration-dependent positive inotropic effect; damaging the EE shifted the terminal portion of the curve upward. Concomitant cholinergic or adrenergic stimulation modified the response to zaprinast into a negative inotropic response. NO and cGMP induced a concentration-dependent biphasic contractile response. The myocardial contractile effects of NO and cGMP were modulated by the status of EE and by concomitant cholinergic or adrenergic stimulation.
    No preview · Article · Apr 1996 · Circulation
  • W J Paulus · P J Vantrimpont · A M Shah
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    ABSTRACT: Similar to endothelial modulation of vascular tone, myocardial contraction may be modulated by cardioactive agents released from the coronary endothelium. To investigate such modulation in humans, we performed invasive assessment of left ventricular (LV) function before, during, and after bicoronary infusion of substance P, which releases nitric oxide from the endothelium. Eight healthy subjects were investigated during diagnostic coronary angiography and eight transplant recipients during annual catheterization. Tip-micromanometer LV pressure was recorded before, during, and after bicoronary (n = 16) and right atrial (n = 14) infusion of substance P (20 pmol/min). LV angiograms (n = 11) were obtained before and at the end of the substance P infusion. At the end of the intracoronary substance P infusion, we observed (1) a fall in LV peak systolic pressure from 147 +/- 16 to 139 +/- 15 mm Hg (P < .01) in healthy subjects and from 147 +/- 25 to 141 +/- 22 mmHg (P < .05) in transplant recipients; (2) a downward and rightward shift of the average LV end-systolic pressure-volume point consistent with depressed systolic performance; and (3) a rise in LV end-diastolic volume at comparable end-diastolic pressure, consistent with increased end-diastolic distensibility. Five minutes after the substance P infusion, LV peak systolic pressure was higher than at baseline in healthy subjects (154 +/- 18 mm Hg; P < .05). Right atrial infusion of substance P did not reproduce these changes. Bicoronary infusion of substance P modulates LV function in humans, probably through paracrine myocardial action of cardioactive agents released from the coronary endothelium.
    No preview · Article · Oct 1995 · Circulation
  • P J Vantrimpont · H Felice · W J Paulus
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    ABSTRACT: The purpose of the study was to evaluate whether infusion of a beta-adrenergic agonist, prior to and during exercise, could compensate for reduced sympathetic stimulation and correct deficient acceleration of left ventricular relaxation, so preventing a rise in left ventricular filling pressures during exercise after cardiac transplantation. Abnormal left ventricular relaxation kinetics can contribute to exercise-induced diastolic dysfunction of the cardiac allograft. This was demonstrated in transplant recipients whose acceleration of left ventricular relaxation during exercise was almost negligible recently and whose elevation of left ventricular end-diastolic pressure was high. Decreased adrenergic tone due to denervation could be involved in deficient left ventricular lusitropic response to exercise, because acceleration of left ventricular relaxation during exercise depends on adequate sympathetic stimulation. Serial supine bicycle exercise was performed at an identical workload in eight transplant recipients while in the control state and during continuous infusion of dobutamine, titrated before exercise to achieve a heart rate matching the heart rate at peak exercise in the control state. During control exercise, heart rate rose from 87 +/- 8 to 104 +/- 12 beats.min-1 (P < 0.05), left ventricular end-diastolic pressure from 14 +/- 5 to 20 +/- 4 mmHg (P < 0.05), left ventricular dP/dtmax from 1374 +/- 172 to 1854 +/- 278 mmHg.s-1 (P < 0.05), and cardiac output from 5.8 +/- 0.9 to 8.5 +/- 1.1 l.min-1 P < 0.05). There was a small but significant decrease of the time constant of left ventricular pressure decay (T) from 42 +/- 6 to 38 +/- 6 ms (P < 0.05). During dobutamine infusion, exercise resulted in a further increase in heart rate from 108 +/- 11 to 122 +/- 17 mmHg (P < 0.05), in cardiac output from 7.4 +/- 0.9 to 10.3 +/- 2.5 l.min-1 (P < 0.05), and in left ventricular dP/dtmax from 2181 +/- 220 to 2620 +/- 214 mmHg.s-1 (P < 0.05). These values were higher than the measurements obtained at the end of the control exercise run (P < 0.05). T failed to change (29 +/- 4 vs 27 +/- 5 mmHg, P > 0.05) and left ventricular end-diastolic pressure increased from 5 +/- 3 to 11 +/- 5 mmHg (P < 0.05) but remained lower than at the end of the control exercise run (11 +/- 5 vs 20 +/- 4 mmHg, P < 0.05). Compensation for reduced sympathetic stimulation by administration of dobutamine improves exercise haemodynamics in cardiac transplant recipients, but cannot prevent the exercise-induced rise in left ventricular end-diastolic pressure and correct deficient acceleration of left ventricular relaxation. Abnormal exercise haemodynamics after heart transplantation are therefore only partly related to deficient sympathetic stimulation.
    No preview · Article · Sep 1995 · European Heart Journal
  • J Bartúnek · P Mohan · W J Paulus · S Cagán
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    ABSTRACT: Over the last years it has become evident that endothelium is one of the most active paracrine organs releasing a number of vasoactive substances. These mediators, by acting on subjacent vascular smooth muscle, play and important role in control of vasomotor tone and of platelets aggregation. The relations between vascular endothelium and cardiovascular risk factors are complex. Functional abnormalities of vascular endothelium are probably segmental and may differ in individual cases. Experimental and clinical study has demonstrated that all cardiac endothelial cells, coronary vascular and endocardial, modulate the performance of underlying myocardium. Modulation of the left ventricular function by endothelial cells constitutes an important autoregulation of muscle-pump performance of the heart by altering the duration of contraction and diastolic function. It is likely that cardiac endothelial cells take part in extrinsic and intrinsic cardiac compensatory mechanisms and, although there is still no direct evidence, they may be closely involved in pathophysiology of heart failure in humans.
    No preview · Article · Mar 1995 · Bratislavske lekarske listy
  • Bernard De Bruyne · Walter J. Paulus · Nico H. J. Pijls
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    ABSTRACT: Presence, extent, and evolution of atherosclerotic coronary narrowings, as well as the anatomic possibilities for revascularization, can be reliably defined at (and only at) selective coronary angiography. The latter remains, therefore, the pivotal diagnostic tool for patients with suspected coronary artery disease. However, in spite of the increasing availability of on-line quantitative coronary angiography, it still holds that the functional (physiologic) consequences of an epicardial coronary narrowing cannot be completely derived from geometric (anatomic) information. Clinical decision making can be particularly difficult in lesions of intermediate severity (40-70% diameter reduction), in postinterventional segments, and in some particular anatomic settings, namely, ostial stenoses, bifurcation lesions, and diffuse atherosclerotic disease. This has led to an explosive growth of new methods for assessing the physiological significance of coronary narrowings documented at angiography. Among them, Doppler blood flow velocitometry and transstenotic pressure gradient measurements have emerged as the only techniques easily applicable in most catheterization laboratories. Here, we briefly review the clinical interest of measuring transstenotic pressure gradients.
    No preview · Article · Nov 1994 · Catheterization and Cardiovascular Diagnosis
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    W J Paulus · P J Vantrimpont · A M Shah
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    ABSTRACT: In isolated mammalian cardiomyocytes, papillary muscle preparations, and ejecting hearts, nitric oxide (NO) or other cyclic GMP-elevating interventions increase diastolic cell length and reduce peak contractile performance by hastening onset of myocardial relaxation. In the present study, the effect of NO on left ventricular (LV) relaxation and diastolic distensibility was investigated in humans. The NO donor substance sodium nitroprusside was infused during cardiac catheterization in the global coronary bed of the LV of patients (n = 13) investigated for chest pain who were without evidence of obstructive coronary artery or other cardiac disease. Sodium nitroprusside was infused intracoronarily at a dosage (< or = 4 micrograms/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed. The effect of this global intracoronary infusion of the NO donor sodium nitroprusside was assessed by sequential LV angiograms and tip-micromanometer pressure recordings. During global intracoronary nitroprusside infusion, there was a decrease in heart rate from 78 +/- 11 to 76 +/- 12 beats per minute (P < .05), in LV peak systolic pressure from 161 +/- 18 to 146 +/- 18 mm Hg (P < .001), and in time to onset of LV relaxation (interval from Q wave on the ECG to LV dP/dtmin) from 432 +/- 36 to 419 +/- 36 milliseconds (P < .01). In 7 patients in whom adequate sequential LV angiograms could be obtained, LV end-diastolic volume increased from 158 +/- 34 to 165 +/- 40 mL (P < .05), whereas LV end-diastolic pressure fell from 18 +/- 5 to 12 +/- 3 mm Hg (P < .02), and in 5 of these 7 patients, a downward shift of the diastolic LV pressure-volume relation was observed. In 5 patients, a right atrial infusion of sodium nitroprusside was performed either before (n = 2) or after the global intracoronary infusion. The decrease in LV peak systolic pressure observed during right atrial infusion was significantly smaller (P < .01) than during global intracoronary infusion. The present study reveals reduced LV pressure development, an LV relaxation-hastening effect, and improved LV diastolic distensibility during global intracoronary infusion of the NO donor substance sodium nitroprusside. These effects appeared to be unrelated to systemic vasodilation or to pericardial constraint and could be explained by a direct myocardial effect of NO, probably through activation of guanylyl cyclase to increase cyclic GMP or through modification of other cellular proteins.
    Preview · Article · May 1994 · Circulation
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    ABSTRACT: Experimental studies have shown that fractional flow reserve (defined as the ratio of maximal achievable flow in a stenotic area to normal maximal achievable flow) can be calculated from coronary pressure measurements only. The objectives of this study were to validate fractional flow reserve calculation in humans and to compare this information with that derived from quantitative coronary angiography. Twenty-two patients with an isolated, discrete proximal or mid left anterior descending coronary artery stenosis and normal left ventricular function were studied. Relative myocardial flow reserve, defined as the ratio of absolute myocardial perfusion during maximal vasodilation in the stenotic area to the absolute myocardial perfusion during maximal vasodilation (adenosine 140 micrograms.kg-1 x min-1 intravenously during 4 minutes) in the contralateral normally perfused area, was assessed by 15O-labeled water and positron emission tomography (PET). Myocardial and coronary fractional flow reserve were calculated from mean aortic, distal coronary, and right atrial pressures recorded during maximal vasodilation. Distal coronary pressures were measured by an ultrathin, pressure-monitoring guide wire with minimal influence on the trans-stenotic pressure gradient. Minimal obstruction area, percent area stenosis, and calculated stenosis flow reserve were assessed by quantitative coronary angiography. There was no difference in heart rate, mean aortic pressure, or rate-pressure product during maximal vasodilation during PET and during catheterization. Percent area stenosis ranged from 40% to 94% (mean, 77 +/- 13%), myocardial fractional flow reserve from 0.36 to 0.98 (mean, 0.61 +/- 0.17), and relative flow reserve from 0.27 to 1.23 (mean, 0.60 +/- 0.26). A close correlation was found between relative flow reserve obtained by PET and both myocardial fractional flow reserve (r = .87) and coronary fractional flow reserve obtained by pressure recordings (r = .86). The correlations between relative flow reserve obtained by PET and stenosis measurements derived from quantitative coronary angiography were markedly weaker (minimal obstruction area, r = .66; percent area stenosis, r = -.70; and stenosis flow reserve, r = .68). Fractional flow reserve derived from pressure measurements correlates more closely to relative flow reserve derived from PET than angiographic parameters. This validates in humans the use of fractional flow reserve as an index of the physiological consequences of a given coronary artery stenosis.
    Full-text · Article · Apr 1994 · Circulation
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    ABSTRACT: The present study was designed to investigate 1) the feasibility and accuracy of coronary pressure measurements with a novel 0.015-in. (0.038 cm) fluid-filled guide wire, and 2) the effect of the guide wire itself on stenosis hemodynamics. To assess the functional results of coronary angioplasty, measurements of the transstenotic pressure gradient have been advocated. However, this gradient is no longer routinely measured because it is not reliable when determined with the angioplasty catheter. A fluid-filled 0.015-in. guide wire to be connected to a conventional pressure transducer was developed. Five wires were tested for their frequency response characteristics and for their accuracy in measuring hydrostatic pressure. In an in vitro model of stenosis (reference diameter 4 mm), the pressure gradient was determined at incremental flow levels for varying stenosis severity with and without a 0.015-in. guide wire through the narrowing. In 37 patients, the transstenotic pressure gradient was measured before and after angioplasty and compared with obstruction area and percent area stenosis as determined by quantitative coronary angiography. The correlation between the actual pressure and the pressure recorded by the guide wire was excellent (r = 0.98) despite a slight underestimation (-3 +/- 5%). Phasic pressure recordings were precluded by a long time constant of 16 +/- 4 s. The presence of the guide wire produced a significant overestimation (> 20%) of the pressure decrease only in cases of tight stenosis (> 90% area reduction). Furthermore, a theoretic model based on the fluid dynamic equation predicted that this overestimation was inversely proportional to the reference diameter of the vessel, yet was only slightly influenced by the flow. The lesion was crossed in all but one patient (97%) and pressure gradient was recorded throughout the study in 34 (94%) of 36 patients. The mean pressure gradient decreased from 30 +/- 19 before to 3 +/- 5 mm Hg after angioplasty (p < 0.01). A curvilinear relation was found between the pressure gradient and both percent area stenosis (r2 = 0.67) and obstruction area (r2 = 0.72). A sharp increase in pressure gradient was noted once the stenosis exceeded 75% area reduction. Mean transstenotic pressure gradients can be easily and reliably recorded with a 0.015-in. fluid-filled guide wire. This ability should facilitate the functional assessment of coronary stenoses of intermediate severity and of immediate postangioplasty results.
    Preview · Article · Aug 1993 · Journal of the American College of Cardiology
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    ABSTRACT: During the initial phase of an ischemic insult, left ventricular (LV) performance depends on the complex interaction between oxygen deprivation, vascular turgor, and accumulation of metabolites. In experimental preparations, low-flow ischemia decreases systolic shortening and increases diastolic LV distensibility, whereas pacing-induced ischemia or hypoxic perfusion produces smaller decreases in systolic shortening but decreases LV diastolic distensibility. The purpose of this study was to investigate the different effects of low-flow ischemia, pacing-induced ischemia, and hypoxemic perfusion on LV performance in humans. In 20 patients with a significant stenosis in the left anterior descending coronary artery, micromanometer-tip LV pressure recordings (n = 20), LV angiography (n = 18), and coronary sinus blood sampling (n = 11) were obtained at rest and during the following conditions: pacing-induced ischemia (PI) (n = 11), low-flow ischemia of balloon coronary occlusion (CO) (n = 20), and hypoxemia induced by balloon coronary occlusion with hypoxemic perfusion distal to the occlusion (CO+P) (n = 11). LV stroke work index fell from 75 +/- 17 g.m at rest to 43 +/- 14 g.m at the end of CO (n = 18; P < .001). In addition, LV stroke work index was lower at the end of CO than during PI (50 +/- 11 vs 77 +/- 15 g.m; n = 11; P < .002) and was lower at the end of CO than at the end of CO+P (35 +/- 7 vs 46 +/- 9 g.m; n = 9; P < .02). LV end-diastolic pressure rose from 16 +/- 5 mm Hg at rest to 23 +/- 6 mm Hg at the end of CO (n = 20; P < .001). However, LV end-diastolic pressure was lower at the end of CO than during PI (20 +/- 5 vs 30 +/- 5 mm Hg; n = 11; P < .002) and was lower at the end of CO than at the end of CO+P (26 +/- 5 vs 34 +/- 7 mm Hg; n = 11; P < .01). LV end-diastolic volume index increased from 75 +/- 14 mL/m2 at rest to 79 +/- 15 mL/m2 at the end of CO (n = 18; P < .05). Left ventricular end-diastolic volume index increased to values similar to those for CO during PI (79 +/- 13 mL/m2; n = 11; P = NS) and at the end of CO+P (78 +/- 14 mL/m2; n = 9; P = NS). Higher values of LV end-diastolic pressure and unchanged values of LV end-diastolic volume index for PI and CO+P, compared with CO, suggested a lower end-diastolic LV distensibility during PI and during hypoxemia, as compared with low-flow ischemia. Upward shifts of individual diastolic LV pressure-volume curves during PI (9 of 11 patients) and at the end of CO+P (7 of 9 patients), compared with CO, were also consistent with lower LV diastolic distensibility during pacing-induced ischemia and during hypoxemia, compared with low-flow ischemia. Coronary sinus lactate, H+, and K+ levels increased after balloon deflation (CO and CO+P) and during pacing (PI). Thus, during low-flow ischemia, LV systolic performance was lower and LV diastolic distensibility larger than during pacing-induced ischemia or hypoxemia. The variable response of the human myocardium to different types of ischemia was probably related to the degree of vascular turgor and accumulation of tissue metabolites.
    Preview · Article · Aug 1993 · Circulation
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    Walter J. Paulus · Pascal J. Vantrimpont · Michel F. Rousseau
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    ABSTRACT: To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.
    Full-text · Article · Jan 1993 · Journal of the American College of Cardiology

Publication Stats

2k Citations
512.53 Total Impact Points


  • 1988-2001
    • OLV Ziekenhuis Aalst
      Alost, Flanders, Belgium
  • 1999
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 1994
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
  • 1990
    • Ghent University
      • Department of Physiology
      Gent, VLG, Belgium
  • 1976-1983
    • University of Antwerp
      • Laboratory of Pathophysiology
      Antwerpen, Flanders, Belgium