Biomedical subjects

Jozef Bartunek

Publications and source records attributed to Jozef Bartunek.

34 records · Page 2Linked to original sources

PubMed2005

Role of beta2 adrenergic receptors in human atherosclerotic coronary arteries.

BACKGROUND: Adrenergic regulation of coronary vasomotion is balanced between alpha1-adrenergic-mediated (alpha1-AR) constriction and beta2-adrenergic-mediated (beta2-AR) relaxation. This study aimed at assessing the role of beta2-ARs in normal, mildly atherosclerotic, and stenotic human coronary arteries. METHODS AND RESULTS: During intracoronary (IC) infusion of increasing doses of the beta2-AR agonist salbutamol (0.15, 0.3, and 0.6 mug/min) and the endothelial vasodilator acetylcholine (1, 3, and 10 microg/min), we measured (1) changes in lumen diameter (LD) by quantitative coronary angiography in 34 normal, 55 mildly atherosclerotic, and 42 stenotic coronary artery segments and (2) changes in average peak velocity (APV) and coronary blood flow (CBF) with the use of Doppler flow wire in 11 normal, 10 mildly atherosclerotic, and 11 stenotic coronary arteries. In 6 of 11 stenotic coronary arteries, the protocol was repeated after an IC bolus (12 microg/kg) of the alpha-adrenergic blocker phentolamine. In 6 of 11 normal coronary arteries, the protocol was repeated after an IC infusion (60 micromol/min) of N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide inhibitor. Neither salbutamol IC infusion nor acetylcholine significantly changed heart rate or blood pressure, whereas L-NMMA slightly increased blood pressure. In normal coronary arteries, salbutamol increased LD (LD max %: 11+/-2, P<0.05), APV (APV max %: 53+/-17, P<0.05), and CBF (CBF max %: 57+/-17, P<0.05), whereas L-NMMA caused a blunted APV (APV max %: 27+/-6, P<0.05) and CBF (CBF max %: 29+/-6, P<0.05) response to salbutamol. In mildly atherosclerotic coronary arteries, the salbutamol increase in LD (LD max %: 10+/-2, P<0.05), APV (APV max %: 33+/-12, P<0.05), and CBF (CBF max %: 37+/-12, P<0.05) was preserved. In stenotic coronary arteries, salbutamol induced a paradoxical reduction in LD (LD max %: -6+/-2, P<0.05), APV (APV max %: -15+/-9, P<0.05), and CBF (CBF max %: -15+/-6, P<0.05), which was no longer observed after phentolamine. Acetylcholine increased LD (LD max %: 14+/-3, P<0.05), APV (APV max %: 61+/-20, P<0.05), and CBF (CBF max %: 67+/-19, P<0.05) in normal coronary arteries. In mildly atherosclerotic coronary arteries, acetylcholine induced a significant reduction in LD (LD max %: -15+/-2, P<0.05) and no changes in APV (APV max %: -6+/-13, P=NS) and CBF (CBF max %: -10+/-13, P=NS). In stenotic coronary arteries, acetylcholine significantly reduced LD (LD max %: -15+/-3, P<0.05), APV (APV max %: -15+/-9, P<0.05), and CBF (CBF max %: -15+/-6, P<0.05). CONCLUSIONS: In severely atherosclerotic coronary arteries, beta2-adrenergic vasodilatation is impaired, and this might contribute to alter the vasomotor balance, further precipitating myocardial ischemia during sympathetic activation.

Acetylcholine↗

PubMed2005

Oxygen uptake efficiency slope, a new submaximal parameter in evaluating exercise capacity in chronic heart failure patients.

BACKGROUND: The oxygen uptake efficiency slope (OUES) is a new submaximal parameter which objectively predicts the maximal exercise capacity in children and healthy subjects. However, the usefulness of OUES in adult patients with and without advanced heart failure remains undetermined. The present study investigates the stability and the usefulness of OUES in adult cardiac patients with and without heart failure. METHODS: Forty-five patients with advanced heart failure (group A) and 35 patients with ischemic heart disease but normal left ventricular ejection fraction (group B) performed a maximal exercise test. PeakVO2 and percentage of predicted peakVO2 were markers of maximal exercise capacity, whereas OUES, ventilatory anaerobic threshold (VAT), and slope VE/VCO2 were calculated as parameters of submaximal exercise. RESULTS: Group A patients had lower peakVO2 (P < .001), lower percentage of predicted peakVO2 (P = .001), lower VAT (P < .05), steeper slope VE/VCO2 (P < .001), and lower OUES (P < .02). Within group A, significant differences were found for VAT, slope VE/VCO2, and OUES (all P < .01) between patients with peakVO2 above and below 14 mL O2/kg/min. Of all the submaximal parameters, VAT correlated best with peakVO2 (r =.814, P < .01) followed by OUES/kg (r = .781, P < .01), and slope VE/VCO2 (r = -.492, P < .001). However, VAT could not be determined in 18 (23%) patients. CONCLUSIONS: OUES remains stable over the entire exercise duration and is significantly correlated with peakVO2 in adult cardiac patients with and without impaired LVEF. Therefore, OUES could be helpful to assess exercise performance in advanced heart failure patients unable to perform a maximal exercise test. Further studies are needed to confirm our hypothesis.

Adult↗

PubMed2005

Non-invasive assessment of coronary flow reserve in idiopathic dilated cardiomyopathy: hemodynamic correlations.

BACKGROUND: Impaired vasodilator myocardial blood flow response has been observed in dilated cardiomyopathy (DCMP). However, the mechanisms responsible for this blunted response are not clear. In the present study, we investigated whether the blunted vasodilator flow response is related to indices of left ventricular performance in patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Eighteen DCMP patients and 12 healthy subjects (C) underwent transoesophageal echocardiography within 48 h from cardiac catheterization. Coronary flow velocity reserve (CFR) was measured in the proximal LAD as the ratio of the peak diastolic coronary flow velocity (Vd-M) after intravenous administration of adenosine to peak baseline diastolic flow velocity (Vd-R). Left ventricular (LV) mass index was positively correlated with baseline coronary diastolic velocity (r=0.415; p=0.043) and inversely correlated with coronary flow reserve (r=-0.570; p=0.003). The baseline coronary diastolic velocity was higher in DCMP vs C (56+/-13 cm/s vs 35+/-12 cm/s; p=0.04). In DCMP pts Vd-R positively correlated with end-diastolic wall stress (r=0.654; p=0.01). Vd increased in both C (96+/-32 cm/s; p<0.05 vs baseline) and DCMP patients (108+/-20 cm/s; p<0.01 vs baseline). The CFR was lower in DCMP patients vs C (1.93+/-0.78 vs 2.99+/-1.01; p=0.009). In DCMP pts CFR was negatively correlated with right atrial pressure (r=-0.595; p=0.015), LVEDP (r=-0.576; p=0.015), pulmonary capillary wedge pressure (PCWP: r=-0.772; p<0.001) and positively with ejection fraction (EF: r=0.683; p=0.003). CONCLUSION: Pts with DCMP have lower CFR compared to controls. This blunted CFR is due to higher baseline coronary flow and reflects higher wall stress. The close relation between CFR and EF, PCWP and LVEDP suggests that not only a higher baseline Vd but also compressive forces due to left ventricular dysfunction might be responsible for the observed blunted adenosine-mediated coronary vasodilation.

Adenosine↗

PubMed2005

Tailored echocardiographic interventricular delay programming further optimizes left ventricular performance after cardiac resynchronization therapy.

BACKGROUND: The aim of cardiac resynchronization therapy is correction of left ventricular (LV) dyssynchrony. However, little is known about the optimal timing of LV and right ventricular (RV) stimulation. OBJECTIVES: The purpose of this study was to evaluate the acute hemodynamic effects of biventricular pacing, using a range of interventricular delays in patients with advanced heart failure. METHODS: Twenty patients with dilated ischemic (n = 12) and idiopathic (n = 8) cardiomyopathy (age 66 +/- 6 years, New York Heart Association class III-IV, LV end-diastolic diameter >55 mm, ejection fraction 22% +/- 18%, and QRS 200 +/- 32 ms) were implanted with a biventricular resynchronization device with sequential RV and LV timing (VV) capabilities. Tissue Doppler echocardiographic parameters were measured during sinus rhythm before implantation and following an optimal AV interval with both simultaneous and sequential biventricular pacing. The interventricular interval was modified by advancing the LV stimulus (LV first) or RV stimulus (RV first) up to 60 ms. For each stimulation protocol, standard echocardiographic Doppler and tissue Doppler imaging (TDI) echo were used to measure the LV outflow tract velocity-time integral, LV filling time, intraventricular delay, and interventricular delay. RESULTS: The highest velocity-time integral was found in 12 patients with LV first stimulation, 5 patients with RV first stimulation, and 3 patients with simultaneous biventricular activation. Compared with simultaneous biventricular pacing, the optimized sequential biventricular pacing significantly increased the velocity-time integral (P <.001) and LV filling time (P = .001) and decreased interventricular delay (P = .013) and intraventricular delay (P = .010). The optimal VV interval could not be predicted by any clinical nor echocardiographic parameter. At 6-month follow-up, the incidence of nonresponders was 10%. CONCLUSION: Optimal timing of the interventricular interval results in prolongation of the LV filling time, reduction of interventricular asynchrony, and an increase in stroke volume. In patients with advanced heart failure undergoing cardiac resynchronization therapy, LV hemodynamics may be further improved by optimizing LV-RV delay.

Aged↗

PubMed2004

Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy.

OBJECTIVES: We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure. BACKGROUND: In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial. METHODS: In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California). RESULTS: A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011). CONCLUSIONS: In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.

Adult↗

PubMed2004

Long-term patency of internal mammary artery bypass grafts: relationship with preoperative severity of the native coronary artery stenosis.

BACKGROUND: Internal mammary artery conduits (IMA) have an excellent long-term patency rate. Nevertheless, graft closure does occur and significantly limits future revascularization options. We sought to investigate the relationship between the long-term patency of IMA with clinical and angiographic parameters. Particularly, the preoperative degree of stenosis of the relevant bypassed coronary vessel was assessed to analyze the importance of chronic competitive flow on the arterial graft closure rate. METHODS AND RESULTS: Consecutive patients in whom occlusion of at least 1 IMA had been documented at angiography (OCC group) were compared with a group of patients with patent IMA grafts (PAT group). The degree of stenosis in the native coronary artery on which the IMA was placed was analyzed by off-line quantitative coronary angiography. Multivariate stepwise logistic regression was used to identify independent clinical and angiographic predictors of occlusion. The OCC group comprised 96 patients (67+/-10 years) with 103 native bypassed arteries analyzed. The PAT group comprised 127 patients (69+/-8 years) with 170 native bypassed arteries analyzed. Both groups were similar except for gender (42% versus 32% female; P=0.04), height (166+/-8 versus 169+/-8 cm; P=0.006), minimum lumen diameter (0.76+/-0.7 versus 0.51+/-0.5; P=0.001), and diameter stenosis of the native artery (73+/-25% versus 84+/-16%; P<0.0001) in OCC versus PAT, respectively. In the multivariate analysis, only percent diameter stenosis was an independent and statistically significant predictor for graft patency. Among IMA placed on coronary arteries with a diameter of stenosis <50% (n=28), the occlusion rate was very high (79%). CONCLUSIONS: The degree of stenosis in the native vessel is a major predictor of internal mammary artery bypass graft patency. The association between nonsignificant stenosis of the native artery and high occlusion rate of the arterial bypass conduit raises concerns about the use of IMA in the treatment of native vessels with only mild or moderate stenosis.

Aged↗

PubMed2004

Brain and other natriuretic peptides: molecular aspects.

Natriuretic peptides have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The family contains of three major peptides-ANP, BNP, CNP-that participate in cardiovascular and cardiorenal homeostasis. Each of these natriuretic peptides binds differentially to specific receptors that signal through different mechanisms. They are cleared enzymatically by neutral endopeptidase as well as by receptor-mediated endocytosis. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide. It is predominantly synthesized in the cardiac ventricles, released as pre-proBNP and then enzymatically cleaved to BNP and the N-terminal portion of BNP(NT-proBNP). Blood measurements of BNP and NT-proBNP have been shown to identify patients with LV dysfunction. This review focuses on the physiology of natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.

Atrial Natriuretic Factor↗

PubMed2004

Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography.

BACKGROUND: Cardiac resynchronization therapy was shown to reverse left ventricular (LV) remodeling in patients with congestive heart failure (CHF). However, the prediction of benefit is controversial. We aimed to investigate predictive factors of LV functional recovery and reversed remodeling after biventricular pacing. METHODS AND RESULTS: Forty-nine consecutive patients with CHF and a wide QRS complex (182+/-32 ms) were studied by echocardiography before resynchronization. Intraventricular and interventricular asynchrony and their combination were assessed by pulsed-wave tissue Doppler imaging from measurements of regional electromechanical coupling times in basal segments of the right and left ventricle. At 6-month follow-up, responders were defined by a relative increase in LV ejection fraction > or =25% compared with baseline (n=27). Receiver operating curve analysis revealed the degree of intraventricular asynchrony (area under the curve=0.77), interventricular asynchrony (area under the curve=0.69), and their combination (area under the curve=0.84) as the best predictors of functional recovery after resynchronization. In addition, the degree of intraventricular and interventricular asynchrony correlated significantly with the improvement of LV ejection fraction (r=0.73, P<0.0001), end-diastolic diameter (r=-0.59, P<0.0001), and end-systolic diameter (r=-0.48, P<0.001) at follow-up. QRS duration and conventional echo-Doppler indices were not predictive of reversed LV remodeling. CONCLUSIONS: In patients with CHF, the degree of intraventricular and interventricular asynchrony and their combination are the best predictive factors of LV functional recovery and reversed remodeling after cardiac resynchronization therapy.

Aged↗

PubMed2004

Tissue doppler imaging predicts recovery of left ventricular function after recanalization of an occluded coronary artery.

OBJECTIVES: We tested the hypothesis that the tissue Doppler imaging (TDI)-derived positive preejection velocity (+VIC) can predict the recovery of contractile function after revascularization in patients with a recent myocardial infarction. BACKGROUND: In experimental studies, the presence and extent of TDI-derived +VIC correlated with the extent of viable myocardium. METHODS: Forty-three patients with a large myocardial infarction and an occluded left anterior descending (n = 38) or dominant right coronary (n = 5) artery were selected. The median duration of occlusion was 24 h. Longitudinal myocardial velocities were recorded at rest by pulsed-wave TDI echocardiography 6 +/- 2 h after revascularization. Functional recovery was defined as an increase in segmental chordal shortening > or =10% at three-month follow-up left ventricular angiogram as compared with baseline. RESULTS: A good quality TDI signal was obtained in 309 of 324 analyzed segments (95.4%). Severe dysfunction was present in 198 segments of which 126 (64%) showed recovery at three-month follow-up. Sampling of all dysfunctional segments lasted 11 +/- 4 min per patient. Sensitivity, specificity, and accuracy of the +VIC to predict segmental recovery were 91%, 71%, and 84%, respectively. The percentage of segments that were dysfunctional at angiography but showed a +VIC correlated with improvement of both global left ventricular ejection fraction (r = 0.60, p = 0.001) and wall motion score index (r = -0.78, p < 0.0001) at follow-up. CONCLUSIONS: Assessment of +VIC by pulsed-wave TDI is a simple and accurate method that predicts recovery of contractile function after revascularization in patients with a recent myocardial infarction.

Angioplasty, Balloon, Coronary↗

PubMed2004

Alpha-adrenergic receptor blockade and hyperaemic response in patients with intermediate coronary stenoses.

BACKGROUND: Maximal hyperaemia is paramount in the diagnosis of patients with coronary artery disease. However in these patients, enhanced alpha-adrenergic microvascular vasoconstriction may preclude adenosine to induce maximal hyperaemia. AIM: To assess the presence and the clinical relevance of residual microvascular resistance after administration of adenosine. METHODS AND RESULTS: Fractional flow reserve (FFR, calculated by coronary pressure measurements during adenosine-induced hyperaemia) was assessed in 85 patients with an intermediate coronary stenosis (mean diameter stenosis of 50+/-1%) and normal left ventricular function which were divided into the following three groups: (a) 33 patients before and after IC bolus of phentolamine, an alpha1-, alpha2-adrenergic blocker; (b) 32 patients before and after IC bolus of urapidil, a selective alpha1-adrenergic blocker; (c) 20 patients before and after IC bolus of saline. Since minimal luminal diameter remained unchanged before and after phentolamine (1.46+/-0.06 vs. 1.47+/-0.06 mm, ns), urapidil (1.46+/-0.06 vs. 1.39+/-0.08, ns), and saline (1.56+/-0.08 vs. 1.55+/-0.08, ns), changes in FFR reflects changes in microvascular resistance. Overall, phentolamine and urapidil induced a slight but significant decrease in FFR (phentolamine: 0.79+/-0.02 vs. 0.77+/-0.02, p<0.05; urapidil: 0.78+/-0.02 vs. 0.75+/-0.02, p<0.05). However, only 6 patients showed a change in FFR from > or = 0.75 to <0.75 and no patients showed a change in FFR from > or = 0.80 to <0.75 that could have influenced clinical decision making. Saline did not induce any change in FFR. Phentolamine and urapidil induced only transient and negligible haemodynamic changes in heart rate and blood pressure. CONCLUSIONS: The administration of alpha-adrenergic blockers in addition to adenosine unmasks a small, yet clinically irrelevant, degree of residual microvascular tone. The consequential changes in FFR values do not significantly affect clinical decision making.

Adrenergic alpha-Antagonists↗

PubMed2004

Hemodynamic effects of inducible nitric oxide synthase and nitrotyrosine generation in heart failure.

OBJECTIVES: The hemodynamic effects of cardiac inducible nitric oxide synthase (iNOS) and of iNOS-mediated peroxynitrite in patients with left ventricular (LV) dysfunction are unclear. The present study investigates the incidence and functional significance of iNOS expression and nitrotyrosine formation in patients with heart failure. METHODS: LV endomyocardial biopsies obtained from 24 patients with heart failure due to idiopathic dilated cardiomyopathy (ejection fraction [EF] <45% and left ventricular end-diastolic volume index [LVEDVI] >102 ml/m2) were analyzed for iNOS and nitrotyrosine. LV contractile performance was assessed by left ventricular ejection fraction (LVEF) and stroke work normalized for end-diastolic pressure (SW/EDP). LV filling pattern was assessed by Doppler E/A wave ratio, deceleration time (DT) of early LV filling and indexed LV end-diastolic volume normalized for EDP as a marker of diastolic distensibility. RESULTS: iNOS immunostaining correlated significantly with nitrotyrosine formation (r = 0.86, p < 0.001). In the whole study group, patients expressing iNOS (n = 13) showed larger LV end-diastolic (173 +/-16 vs 128 +/- 9 ml/m2, p = 0.031) and end-systolic volume indices (110 +/- 16 vs 61 +/- 9 ml/m2, p = 0.018) and similar LVEDP (18 +/- 2 vs 21 +/- 2 mm Hg, p = 0.227). In patients with advanced heart failure and reduced pre-load reserve (LVEDP > 16 mm Hg, n = 18), iNOS protein and nitrotyrosine formation correlated positively with LVSW/EDP (r = 0.65, p = 0.03 and r = 0.64, p = 0.04, respectively), DT (r = 0.96, p < 0.01 and r = 0.88, p < 0.01, respectively) and inversely with E/A (r = -0.82, p < 0.01 and r = -0.88, p < 0.01, respectively). In addition, nitrotyrosine formation correlated positively with LVEDVI/EDP (r = 0.64, p = 0.02). Advanced iNOS-positive heart failure patients had a higher LVEDVI/EDP compared with iNOS-negative patients (5.30 +/- 0.64 vs 3.13 +/- 0.34 ml/mm Hg x m2, p = 0.02). CONCLUSIONS: In heart failure, iNOS protein expression is associated with nitrotyrosine formation. Although iNOS-positive patients are generally characterized by larger LV volume and depressed function, the preserved NO generation appears to be associated with higher cardiac work due to the preserved Frank-Starling relationship in end-stage heart failure.

Adult↗

PubMed2003

Effects of intravenous dobutamine on coronary vasomotion in humans.

OBJECTIVES: We sought to investigate the vascular mechanisms of dobutamine-induced myocardial ischemia. BACKGROUND: Dobutamine stress is often used as a surrogate for exercise. The effects of dobutamine on the epicardial arteries are incompletely understood and possibly different from those of physical exercise. METHODS: Intravenous (IV) dobutamine (40 microg/kg per min) was administered in 19 patients with normal, 23 patients with mildly atherosclerotic, and 12 patients with stenotic coronary arteries. In another two groups of patients with stenotic arteries, IV dobutamine was preceded by 1) an intracoronary (IC) bolus of the alpha-adrenergic blocker phentolamine (12 microg/kg, n = 12); and 2) an IC infusion of the nitric oxide substrate L-arginine (150 micromol/l per min for 20 min, n = 11). Intravenous saline instead of dobutamine was infused into eight patients with normal arteries. After dobutamine (or saline), an IC bolus of isosorbide dinitrate (ISDN, 0.2 mg) was given. Coronary vasomotion was evaluated by quantitative coronary angiography on angiograms obtained after each dose of dobutamine, saline, phentolamine, L-arginine, and ISDN. RESULTS: Dobutamine increased the rate-pressure product and heart rate similarly in all patients except those who received saline. Dobutamine induced vasodilation in normal (change in luminal diameter [DeltaLD] vs. baseline: 19 +/- 2%) and in mildly atherosclerotic arteries (DeltaLD: 8 +/- 2%, p < 0.05 vs. normal). In stenotic arteries, dobutamine did not induce significant vasomotion (DeltaLD: -3 +/- 3%); the latter was improved by L-arginine (DeltaLD: 10 +/- 3%, p < 0.05 vs. stenotic arteries) and fully restored by phentolamine (DeltaLD: 19 +/- 3%, p < 0.05 vs. stenotic arteries). CONCLUSIONS: Endothelial dysfunction and enhanced alpha-adrenergic tone contribute to the loss of dobutamine-induced vasodilation in coronary atherosclerosis. In contrast to physical exercise, dobutamine does not induce "paradoxical vasoconstriction" of atherosclerotic coronary arteries.

Adrenergic beta-Agonists↗

PubMed2003

Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans.

BACKGROUND: Inducing both maximal and steady-state coronary hyperemia is of clinical importance to take full advantage of fractional flow reserve measurements. The present study compares different dosages and routes of administration of adenosine 5'-triphosphate (ATP), adenosine, contrast medium, and papaverine regarding their potential to achieve both maximal and steady-state hyperemia. METHODS AND RESULTS: In 21 patients with an isolated coronary stenosis, coronary vasodilation was induced successively by papaverine (20 mg intracoronary), adenosine (20 and 40 microg intracoronary), ATP (20 and 40 microg intracoronary), iohexol (6 mL intracoronary), adenosine or ATP through an antecubital vein (140 and 180 microg x kg(-1) x min(-1)), or adenosine or ATP through a femoral vein (140 and 180 microg x kg(-1) x min(-1)). Because vessel dimensions did not change, the ratio of distal coronary pressure (Pd) to aortic pressure (Pa) was used as an index of myocardial resistance. Pd/Pa was 0.77+/-0.21 at rest and decreased to 0.61+/-0.21 after papaverine. Pd/Pa decreased to a similar level with all other vasodilators, except with contrast medium (0.68+/-0.21; P<0.01 versus papaverine). Steady-state hyperemia could only be obtained by intracoronary papaverine and by intravenous ATP or adenosine. In another 23 patients, an intravenous infusion of ATP was varied from 0 to 280 microg x kg(-1) x min(-1). At doses >140 microg x kg(-1) x min(-1), there was neither a further decrease in Pd/Pa ratio nor a further increase in coronary flow velocities. CONCLUSIONS: Provided sufficient dosages are used, ATP, adenosine, and papaverine (but not contrast medium) induce maximal hyperemia and are therefore suitable to assess fractional flow reserve. Only intracoronary papaverine and intravenous ATP or adenosine induce steady-state hyperemia enabling a pressure pullback maneuver that is useful in assessing diffuse coronary atherosclerosis.

Adenosine↗

PubMed2002

Deoxyribonucleic acid damage/repair proteins are elevated in the failing human myocardium due to idiopathic dilated cardiomyopathy.

OBJECTIVES: The study investigated the expression and relationship of deoxyribonucleic acid (DNA) repair enzymes with hemodynamic and nitric oxide (NO)-mediated stress in the failing myocardium. BACKGROUND: The role of apoptosis in human heart failure is controversial. Experimental studies suggested that NO-mediated stress modulates apoptosis of the cardiac myocytes. Of note, DNA repair enzymes such as redox factor/apurinic/apyridimine endonuclease Ref-1 protein, proliferative cell nuclear antigen (PCNA), the poly (ADP-ribose) polymerase (PARP), and DNA-protein kinase (DNA-PK) determine the cell fate after the DNA damage. METHODS: Left ventricular (LV) endomyocardial biopsies from 23 patients with dilated cardiomyopathy were analyzed by immunohistochemistry. RESULTS: Terminal deoxynucleotidyltransferase-mediated biotin-dUTP nick-end labeling (TUNEL) or cleaved caspase-3 and cleaved PARP could not be detected. The number of Ref-1-positive myocytes tended to be higher in patients with LV ejection fraction (EF) < or =35% versus LV EF >35% (21.23 +/- 4.8% vs. 13.8 +/- 5.8%, p = 0.1). The PCNA (7.1 +/- 2.8% vs. 0.9 +/- 0.6%, p = 0.05) and DNA-PK expressions (39.5 +/- 5.4% vs. 8.6 +/- 5.5%, p < 0.01) were higher in patients with LVEF < or =35% vs. LVEF >35%. The PCNA, Ref-1, and DNA-PK expression correlated with the LV end-systolic wall stress (r = 0.61, p < 0.01; r = 0.52, p < 0.01; and r = 0.73, p < 0.001, respectively). In addition, the PCNA and DNA-PK expression correlated with inducible NO synthase (r = 0.41, p = 0.05, and r = 0.53, p < 0.01, respectively). CONCLUSION: In this study, apoptosis could not be detected in the failing myocardium owing to idiopathic dilated cardiomyopathy. In contrast, failing myocardium was characterized by active DNA repair that was associated with elevated LV wall stress and activation of the inducible NO synthase.

Adult↗

PubMed2002

Coronary thermodilution to assess flow reserve: validation in humans.

BACKGROUND: Guide wire-based simultaneous measurement of fractional flow reserve (FFR) and coronary flow reserve (CFR) is important to understand microvascular disease of the heart. The aim of this study was to investigate the feasibility of simultaneous measurement of FFR and CFR by one pressure-temperature sensor-tipped guide wire with the use of coronary thermodilution and to compare CFR by thermodilution (CFR(thermo)) with simultaneously measured Doppler CFR (CFR(Doppl)). METHODS AND RESULTS: In 103 coronary arteries in 50 patients, a pressure-temperature sensor-tipped 0.014-inch floppy guide wire and a 0.014-inch Doppler guide wire were introduced. Both normal vessels and a wide range of stenotic vessels were included. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the coronary artery were obtained in triplicate, both at baseline and at intravenous adenosine-induced maximum hyperemia. After adequate curve-fitting, CFR(thermo) was calculated from the ratio of inverse mean transit times and compared with CFR(Doppl) calculated by velocities at hyperemia and baseline. Adequate sets of thermodilution curves and corresponding CFR(thermo) could be obtained in 87% of the arteries versus 91% for Doppler CFR and 100% for FFR. CFR(thermo) correlated fairly well to CFR(Doppl) (CFR(thermo)=0.84 CFR(Doppl)+0.17; r=0.80; P<0.001), although individual differences of >20% between both indexes were seen in a quarter of all arteries. CONCLUSIONS: This study shows the feasibility of simultaneous measurement of FFR (by coronary pressure) and CFR (by coronary thermodilution) in humans by one single guide wire in a practical and straightforward way and will facilitate assessment of microvascular disease.

Blood Flow Velocity↗

PubMed2002

Neutral endopeptidase is activated in cardiomyocytes in human aortic valve stenosis and heart failure.

BACKGROUND: The regulation of the cardiac neutral endopeptidase (EC 24.10, NEP) that degrades bradykinin and natriuretic peptides has been investigated in human cardiac hypertrophy and heart failure. Methods and Results- NEP mRNA was quantitated by real-time polymerase chain reaction (PCR) in left ventricular biopsies from patients with aortic valve stenosis (AS, n=19) and heart failure due to dilated cardiomyopathy (DCM, n=14), and control subjects with normal systolic function (CON, n=14). Left ventricular NEP mRNA content was increased 3-fold in AS (P<0.005) and 4.1-fold in DCM (P<0.002). The increase in NEP mRNA was related to the increase in end diastolic pressure in AS and DCM. In a second series, myocardial NEP enzymatic activity was determined. It increased 3.6-fold in AS (P<0.02) and 4-fold in DCM (P<0.002). NEP was localized in the myocardium by immunofluorescence microscopy and in situ PCR to myocytes and nonmyocyte areas and cells. CONCLUSIONS: Elevated cardiac NEP activity in pressure loaded and failing human hearts may increase the local degradation of bradykinin and natriuretic peptides.

Aortic Valve Stenosis↗