Ultrafast and whole-body cooling with total liquid ventilation induces favorable neurological and cardiac outcomes after cardiac arrest in rabbits.

BACKGROUND: In animal models of cardiac arrest, the benefit afforded by hypothermia is closely linked to the rapidity of the decrease in body temperature after resuscitation. Because total liquid ventilation (TLV) with temperature-controlled perfluorocarbons induces a very rapid and generalized cooling, we aimed to determine whether this could limit the post-cardiac arrest syndrome in a rabbit model. We especially focused on neurological, cardiac, pulmonary, liver and kidney dysfunctions. METHODS AND RESULTS: Anesthetized rabbits were submitted to either 5 or 10 minutes of untreated ventricular fibrillation. After cardiopulmonary resuscitation and resumption of a spontaneous circulation, the animals underwent either normothermic life support (control) or therapeutic hypothermia induced by TLV. The latter procedure decreased esophageal and tympanic temperatures to 32°C to 33°C within only 10 minutes. After rewarming, the animals submitted to TLV exhibited an attenuated neurological dysfunction and decreased mortality 7 days later compared with control. The neuroprotective effect of TLV was confirmed by a significant reduction in brain histological damages. We also observed limitation of myocardial necrosis, along with a decrease in troponin I release and a reduced myocardial caspase 3 activity, with TLV. The beneficial effects of TLV were directly related to the rapidity of hypothermia induction because neither conventional cooling (cold saline infusion plus external cooling) nor normothermic TLV elicited a similar protection. CONCLUSIONS: Ultrafast cooling instituted by TLV exerts potent neurological and cardiac protection in an experimental model of cardiac arrest in rabbits. This could be a relevant approach to provide a global and protective hypothermia against the post-cardiac arrest syndrome.

Pentraxin 3 in primary percutaneous coronary intervention for ST elevation myocardial infarction is associated with early irreversible myocardial damage : Kinetic profile, relationship to interleukin 6 and infarct size.

BACKGROUND: The inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size. METHODS: PTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI). RESULTS: PTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0-72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006). CONCLUSIONS: PTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.

Repeated coronary artery occlusions during routine balloon angioplasty do not induce myocardial preconditioning in humans.

OBJECTIVES: The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty induce a myocardial ischemic protective effect. BACKGROUND: In animals, brief coronary artery occlusions preceding a more prolonged occlusion result in reduced infarct size. Whether myocardial protection against ischemia could also occur in humans during angioplasty remains controversial. METHODS: Thirteen patients with a proximal left anterior descending coronary artery stenosis with no angiographic collateral circulation underwent percutaneous transluminal coronary artery balloon angioplasty. Three 120-s balloon inflations separated by a 5-min equilibration period were performed. For each inflation, intracoronary ST segment modifications, septal wall thickening (M-mode echocardiography), left ventricular pressures and time derivatives were measured at baseline and at 30, 60 and 90 s after balloon inflation and 120 s after balloon deflation. RESULTS: Intracoronary electrocardiographic analysis showed that the time course of the maximal ST segment elevation was identical at each inflation, as were wall motion changes assessed by the decrease in septal wall thickening. For the first and last inflations, peak positive dP/dt decreased significantly by 13 +/- 9% (mean +/- SD) and 14 +/- 13%, whereas peak negative dP/dt increased by 23 +/- 15% and 22 +/- 10%, respectively (all p < 0.01 from baseline values). The relaxation time constant, tau, was altered similarly during the different inflations, from 44 +/- 6 to 74 +/- 13 ms and from 57 +/- 13 to 77 +/- 13 ms (all p < 0.001) for the first and last inflations, respectively. Left ventricular end-diastolic pressure increased to the same level after each inflation. In contrast to other hemodynamic variables, tau and left ventricular end-diastolic pressure did not return to baseline values in between the inflations, which may be due to myocardial stunning. CONCLUSIONS: In patients with proximal left anterior descending coronary artery stenosis and no evidence of collateral circulation, brief periods of ischemia, such as those used during routine coronary balloon angioplasty, do not provide any protection against myocardial ischemia.

Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis.

OBJECTIVES: This study was designed to evaluate the relation between the velocity of flow propagation and left ventricular relaxation by using color M-mode Doppler echocardiography to analyze flow propagation in the left ventricle. BACKGROUND: Noninvasive attempts to identify alterations in left ventricular relaxation have been hampered because both the relaxation rate and left atrial filling pressure are the determinants of peak early velocity and filling rate. METHODS: Color M-mode velocity data were transferred to a microcomputer and compared with conventional pulsed Doppler data to assess the ability of color M-mode echocardiography to analyze velocity field properties. The velocity of flow propagation was measured as the slope of the flow wave front during early filling in normal subjects (n = 29) and in patients with disease that alters relaxation (dilated cardiomyopathy [n = 31], ischemic cardiomyopathy [n = 8], hypertrophic cardiomyopathy [n = 5], systemic hypertension [n = 22] and aortic valve disease [n = 25]). In nine patients with end-stage dilated cardiomyopathy, echocardiographic and left heart catheterization data were obtained at baseline and during intracoronary dobutamine infusion. RESULTS: Color M-mode and pulsed Doppler echocardiographic data were highly correlated (n = 217, r = 0.94, p less than 0.0001, velocity range 0.2 to 1.5 m/s). The velocity of flow propagation was lower in patients than in normal subjects (0.46 +/- 0.15 vs. 0.84 +/- 0.11 m/s, p less than 0.0001). The decrease was significant in all disease forms with or without left ventricular dilation. The velocity of flow propagation was related to peak early velocity in normal subjects (p less than 0.001) but not in patients. It varied inversely with the isovolumetric relaxation time constant during dobutamine infusion and the two variables were highly correlated (p less than 0.0001). CONCLUSIONS: The velocity of flow propagation during early filling seems to be highly dependent on the left ventricular relaxation rate and could be an important tool in studying diastolic function.

Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine echocardiography.

OBJECTIVES: We sought to assess risk stratification by using dobutamine stress echocardiography (DSE) in patients with aortic stenosis (AS) and severe left ventricular (LV) dysfunction. BACKGROUND: Few data are available on risk stratification for valve replacement in patients with AS, LV dysfunction and low transvalvular gradients. METHODS: Low-dose DSE was performed in 45 patients (16 women and 29 men; median [quartile range] age in years: 75 [69 to 79]; left ventricular ejection fraction: 0.29 [0.23 to 0.32]; aortic valve area [cm2]: 0.7 [0.5 to 0.8]; mean transaortic gradient [mm Hg]: 26 [21 to 33]). Patients were classified into two groups: group I (n = 32, LV contractile reserve on DSE) and group II (n = 13, no contractile reserve). Valve replacement was performed in 24 and 6 patients in groups I and II, respectively. RESULTS: Perioperative mortality was 8% in group I and 50% in group II (p = 0.014). Survival at five years after the operation was 88% in group I. Compared with medical therapy, valve surgery was associated with better long-term survival in group I (hazard ratio for death [HR-D] 0.13, 95% confidence interval [CI] 0.002 to 0.49) and reduced survival in group II (HR-D 19.6, 95% CI 2.7 to 142). The effect of valve surgery on survival remained significant in both groups after adjustment for age, diabetes, respiratory disease and hypertension. Medical therapy had the same effect in both groups. CONCLUSIONS: In patients with AS, LV dysfunction and low transvalvular gradients, contractile reserve on DSE is associated with a low operative risk and good long-term prognosis after valve surgery. In contrast, operative mortality remains high in the absence of contractile reserve.

Endogenous sodium-potassium-chloride cotransport inhibitor in congestive heart failure.

OBJECTIVES: This study sought to evaluate the relation, if any, between fluid overload in congestive heart failure (CHF) and a newly discovered endogenous natriuretic factor acting like loop diuretic drugs: cotransport inhibitory factor (CIF). BACKGROUND: The humoral mechanisms regulating volume overload in CHF are not fully understood. Therefore, we investigated whether there is a role for CIF in this pathologic condition. METHODS: Plasma and urinary CIF levels were investigated in 23 patients with chronic CHF and compared with changes in plasma atrial natriuretic peptide (ANP). Twelve patients without CHF served as control subjects. RESULTS: CHF was associated with a highly significant threefold increase in both plasma CIF levels (mean +/- SD 7.10 +/- 3.01 vs. 2.28 +/- 0.92 U/ml, p < 0.0001) and urinary CIF excretion (7,849 +/- 3,600 vs. 2,351 +/- 1,297 U/day, p < 0.0001) with respect to patients without CHF. CIF increased as a function of impairment in left ventricular ejection fraction (r = -0.703, p < 0.0001) and the severity of clinical status. Plasma ANP was also increased in patients with CHF, although to a lesser extent (68%, p = 0.0501) than plasma CIF, and was also significantly correlated with left ventricular ejection fraction (r = -0.552, p = 0.0004). CONCLUSIONS: Plasma and urinary CIF activities were strongly and very significantly increased in chronic CHF. In addition to ANP, this long-term natriuretic agent may be of potential importance in reducing fluid overload in CHF.

Effects of bradykinin on coronary blood flow and vasomotion in transplant patients.

OBJECTIVES: To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine. BACKGROUND: Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs. METHODS: Sixteen HTXs were compared 3.6 +/- 1.7 months after transplantation to seven control subjects. Coronary flow velocity was measured using guide-wire Doppler. Diameters (D) of three segments of the left coronary artery and coronary blood flow (CBF) were assessed at baseline, after 3-min infusions of increasing bradykinin doses (50, 150 and 250 ng/min) then of increasing acetylcholine doses (estimated blood concentrations of 10(-8), 10(-7) and 10(-6) M). RESULTS: Bradykinin induced similar dose-dependent increases in D and CBF in both groups: D was 11 +/- 12%, 19 +/- 14% and 22 +/- 16% (all p < 0.0001), and CBF was 50 +/- 40%, 130 +/- 68% and 186 +/- 77% (all p < 0.0001). Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in HTX, as well as a marked increase in CBF in both groups. Acute allograft rejection, present in 8 of the 16 HTXs, did not modify responses to bradykinin, but was associated with a smaller CBF increase in response to acetylcholine (p < 0.05). CONCLUSIONS: The coronary vasodilating effects of bradykinin are preserved early after heart transplantation, even in the presence of acute allograft rejection. Although there is an abnormal vasoconstricting response to acetylcholine reflecting endothelium dysfunction, the endothelium remains a functionally active organ in heart transplant recipients.

Alteration of left ventricular diastolic function during coronary angioplasty-induced ischemia: a color M-mode Doppler study.

OBJECTIVES: The aim of this study was to assess the effects of ischemia on diastolic function by analyzing flow propagation velocity with color M-mode Doppler echocardigraphy. BACKGROUND: Color M-mode Doppler echocardiography has been proposed as a method of assessing left ventricular filling. METHODS: Color M-mode Doppler echocardiography and measurement of hemodynamic data were performed simultaneously at baseline and during angioplasty-induced ischemia. Tau was compared with flow propagation velocity. Late diastolic indexes, left ventricular pressure and flow cessation time were also investigated. RESULTS: During ischemia, left ventricular relaxation rate (tau) increased, whereas flow propagation velocity decreased, from (mean +/- SD) 46.8 +/- 10 ms to 72.6 +/- 18.3 ms and from 59.8 +/- 15.8 cm/s to 30 +/- 8 cm/s, respectively (all p < 0.0001). The maximal slowing of flow propagation velocity was observed 20 to 30 s after the beginning of the inflation, coexisting with a notch on the ascending limb of the negative rate of rise of the left ventricular pressure (dP/dt) curve. Flow propagation velocity was correlated with tau both at baseline (r = 0.53, p < 0.05) and during inflation (r = 0.53, p < 0.03). Left ventricular end-diastolic pressure increased during ischemia from 13.5 +/- 8 mm Hg at baseline to 27.5 +/- 7 mm Hg, while a premature cessation of the entering flow occurred -13.8 +/- 23 ms before the next Q wave onset, compared with 4.5 +/- 19.6 ms after the Q wave onset at baseline (all p < 0.0001). CONCLUSIONS: The analysis of flow propagation velocity showed that early filling is highly dependent on left ventricular relaxation rate, particularly through the phenomenon of asynchrony. During ischemia, the premature cessation of late filling is associated with increased diastolic pressures.

Prediction of functional recovery of viable myocardium after delayed revascularization in postinfarction patients: accuracy of dobutamine stress echocardiography and influence of long-term vessel patency.

OBJECTIVES: We sought to evaluate dobutamine stress echocardiography (DSE) for predicting recovery of viable myocardium after revascularization with cineangiography as a gold standard for left ventricular (LV) function. We studied the influence of late vessel reocclusion on regional LV function. BACKGROUND: Dobutamine stress echocardiography is a well established evaluation method for myocardial viability assessment. In previous studies the reference method for assessing LV recovery was echocardiography, long-term vessel patency has not been systematically addressed. METHODS: Sixty-eight patients with a first acute myocardial infarction (AMI) and residual stenosis of the infarct related artery (IRA) underwent DSE (mean +/- standard deviation) 21 +/- 12 days after AMI to evaluate myocardial viability. Revascularization of the IRA was performed in 54 patients by angioplasty (n = 43) or bypass grafting (n = 11). Coronary angiography and LV cineangiography were repeated at four months to assess LV function and IRA patency. RESULTS: Sensitivity and specificity of DSE for predicting myocardial recovery after revascularization were 83% and 82%. In the case of late IRA patency, specificity increased to 95%, whereas sensitivity remained unchanged. In the 16 patients with myocardial viability and late IRA patency, echocardiographic wall motion score index decreased after revascularization from 1.83 +/- 0.15 to 1.36 +/- 0.17 (p = 0.0001), and left ventricular ejection fraction (LVEF) increased from 0.52 +/- 0.06 to 0.57 +/- 0.06 (p = 0.0004), whereas in five patients, reocclusion of the IRA prevented improvement of segmental or global LV function despite initially viable myocardium. CONCLUSIONS: Dobutamine stress echocardiography is reliable to predict recovery of viable myocardium after revascularization in postinfarction patients. Late reocclusion of the IRA may prevent LV recovery and influence the accuracy of DSE.

The French Randomized Optimal Stenting Trial: a prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography. F.R.O.S.T. Study Group.

OBJECTIVES: We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS: Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

Sympathetic nerve alterations assessed with 123I-MIBG in the failing human heart.

UNLABELLED: Norepinephrine (NE) reuptake function is impaired in heart failure and this may participate in myocyte hyperstimulation by the neurotransmitter. This alteration can be assessed by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. METHODS: To determine whether the impairment of neuronal NE reuptake was reversible after metoprolol therapy, we studied 18 patients (43+/-7 y) with idiopathic dilated cardiomyopathy who were stabilized at least for 3 mo with captopril and diuretics. Patients underwent, before and after 6 mo of therapy with metoprolol, measurements of radionuclide left ventricular ejection fraction (LVEF), maximal oxygen consumption and plasma NE concentration. The cardiac adrenergic innervation function was scintigraphically assessed with MIBG uptake and release measurements on the planar images obtained 20 min and 4 h after tracer injection. To evaluate whether metoprolol had a direct interaction with cardiac MIBG uptake and release, six normal subjects were studied before and after a 1-mo metoprolol intake. RESULTS: In controls, neither cardiac MIBG uptake and release nor circulating NE concentration changed after the 1-mo metoprolol intake. Conversely, after a 6-mo therapy with metoprolol, patients showed increased cardiac MIBG uptake (129%+/-10% versus 138%+/-17%; P = 0.009), unchanged cardiac MIBG release and decreased plasma NE concentration (0.930+/-412 versus 0.721+/-0.370 ng/mL; P = 0.02). In parallel, patients showed improved New York Heart Association class (2.44+/-0.51 versus 2.05+/-0.23; P = 0.004) and increased LVEF (20%+/-8% versus 27%+/-8%; P = 0.0005), whereas maximal oxygen uptake remained unchanged. CONCLUSION: Thus, a parallel improvement of myocardial NE reuptake and of hemodynamics was observed after a 6-mo metoprolol therapy, suggesting that such agents may be beneficial in heart failure by directly protecting the myocardium against excessive NE stimulation.

Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure.

The prognostic value of 123I-metaiodobenzylguanidine (MIBG) imaging was compared with that of other noninvasive cardiac imaging indices in ninety patients (mean age = 52 +/- 7 yr) suffering from either ischemic (n = 24) or idiopathic (n = 66) cardiomyopathy. Patients had different measurements taken: cardiac MIBG uptake, radionuclide left ventricular ejection fraction, x-ray cardiothoracic ratio and echographic M-Mode data. Cardiac MIBG uptake was assessed as the heart-to-mediastinum activity ratio measured on the chest anterior view image obtained 4 hr after intravenous injection. The patients then had follow-up for 1-27 mo, at which time 10 patients had transplants, 22 had died and 58 were still alive. Data from patients with transplants were not used in the analysis, in which multivariate stepwise regression discriminant analysis showed that cardiac MIBG uptake was more potent to predict survival than other indices: H/M (p less than 0.0001), x-ray cardiothoracic ratio (p = 0.0017), echographic end-diastolic diameter (p = 0.0264) and radionuclide left ventricular ejection fraction (p = 0.0301). Moreover, multivariate life table analysis showed that cardiac MIBG uptake was also the best predictor for life duration: H/M (p = 0.0001), radionuclide left ventricular ejection fraction (p = 0.0098) and x-ray cardiothoracic ratio (p = 0.0139); echographic data were not useful. Thus, cardiac MIBG imaging may be helpful for heart transplantation decision making in patients with heart failure.

Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy.

UNLABELLED: Alterations of cardiac sympathetic innervation are likely to contribute to fatal outcomes in patients with heart failure. These alterations can be evaluated noninvasively by 123I-metaiodoben-zylguanidine (MIBG) imaging. METHODS: The hypothesis that impaired cardiac sympathetic innervation, as assessed using MIBG imaging, is related to adverse outcomes was tested in 112 patients with heart failure resulting from idiopathic cardiomyopathy. Main inclusion criteria were New York Heart Association classes II-IV and radionuclide left ventricular ejection fraction (LVEF) < 40%. Patients were assessed for cardiac MIBG uptake, circulating norepinephrine concentration, LVEF, peak Vo2, x-ray cardiothoracic ratio, M-mode echographic end-diastolic diameter and right-sided heart catheterization parameters. RESULTS: During a mean follow-up of 27 +/- 20 mo, 19 patients had transplants, 25 died of cardiac death (8 sudden deaths), 2 died of noncardiac death and 66 survived without transplantation. The only independent predictors for mortality were low MIBG uptake (P < 0.001) and LVEF (P = 0.02) when using multivariate discriminant analysis. Moreover, MIBG uptake (P < 0.001) and circulating norepinephrine concentration (P = 0.001) were the only independent predictors for life duration when using multivariate life table analysis. CONCLUSION: Impaired cardiac adrenergic innervation as assessed by MIBG imaging is strongly related to mortality. MIBG imaging may help risk stratify patients with heart failure resulting from idiopathic dilated cardiomyopathy.

Validation of myocardial perfusion reserve measurements using regularized factor images of H(2)(15)O dynamic PET scans.

UNLABELLED: The use of H(2)(15)O PET scans for the measurement of myocardial perfusion reserve (MPR) has been validated in both animal models and humans. Nevertheless, this protocol requires cumbersome acquisitions such as C(15)O inhalation or (18)F-FDG injection to obtain images suitable for determining myocardial regions of interest. Regularized factor analysis is an alternative method proposed to define myocardial contours directly from H(2)(15)O studies without any C(15)O or FDG scan. The study validates this method by comparing the MPR obtained by the regularized factor analysis with the coronary flow reserve (CFR) obtained by intracoronary Doppler as well as with the MPR obtained by an FDG acquisition. METHODS: Ten healthy volunteers and 10 patients with ischemic cardiopathy or idiopathic dilated cardiomyopathy were investigated. The CFR of patients was measured sonographically using a Doppler catheter tip placed into the proximal left anterior descending artery. The mean velocity was recorded at baseline and after dipyridamole administration. All subjects underwent PET imaging, including 2 H(2)(15)O myocardial perfusion studies at baseline and after dipyridamole infusion, followed by an FDG acquisition. Dynamic H(2)(15)O scans were processed by regularized factor analysis. Left ventricular cavity and anteroseptal myocardial regions of interest were drawn independently on regularized factor images and on FDG images. Myocardial blood flow (MBF) and MPR were estimated by fitting the H(2)(15)O time-activity curves with a compartmental model. RESULTS: In patients, no significant difference was observed among the 3 methods of measurement-Doppler CFR, 1.73 +/- 0.57; regularized factor analysis MPR, 1.71 +/- 0.68; FDG MPR, 1.83 +/- 0.49-using a Friedman 2-way ANOVA by ranks. MPR measured with the regularized factor images correlated significantly with CFR (y = 1.17x - 0.30; r = 0.97). In the global population, the regularized factor analysis MPR and FDG MPR correlated strongly (y = 0.99x; r = 0.93). Interoperator repeatability on regularized factor images was 0.126 mL/min/g for rest MBF, 0.38 mL/min/g for stress MBF, and 0.34 for MPR (19% of mean MPR). CONCLUSION: Regularized factor analysis provides well-defined myocardial images from H(2)(15)O dynamic scans, permitting an accurate and simple measurement of MPR. The method reduces exposure to radiation and examination time and lowers the cost of MPR protocols using a PET scanner.

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of exercise and cold pressor test on the vasomotor response of normal and atherosclerotic coronary arteries and their relation to the flow-mediated mechanism.

This study was designed to assess the vasomotor response of coronary arteries to exercise and the cold pressor test, and its relationships with the endothelium-mediated dependent mechanism. Twenty-two patients were entered in the study. Group I was composed of 12 patients with a total cholesterol level < 200 mg/dl associated with angiographically smooth, normal coronary arteries. Group 2 consisted of 10 patients with both a cholesterol level > 240 mg/dl and angiographic luminal irregularities of the left anterior descending coronary artery. Coronary blood flow was assessed by a 0.018-inch tip guidewire during Doppler ultrasonography, and analysis of the coronary arterial dimension of the midportion of the left anterior descending coronary artery was performed by quantitative coronary angiography. Catecholamine concentrations were assessed at the different stages of the protocol. The rate-pressure product increased during both the cold pressure test and exercise (p < 0.001). Coronary blood flow velocity increased during the cold pressor and exercise tests by 24.5 +/- 10% and 72 +/- 42%, respectively (p < 0.001), and by 127 +/- 62% (p < 0.0001) after administration of papaverine. In group 1, the cold pressor test had a more pronounced vasodilating effect on epicardial coronary arteries (+11.2 +/- 16%) compared with group 2 (-2 +/- 9%, p < 0.05). Similarly, exercise had a vasodilating action in group 1 (11.3 +/- 15%) compared with group 2 (-1.9 +/- 8%, p < 0.05). Both responses were highly correlated (r = 0.92, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Prehospital use of APSAC: results of a placebo-controlled study.

Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. To give treatment before admission to a coronary care unit, responsibility needs to be transferred from cardiologists to other physicians working in mobile care units. We conducted a 2-part feasibility study to investigate this strategy. Part 1 evaluated the diagnostic accuracy of mobile care unit physicians. Results from this study indicate that with regard to the diagnosis of acute myocardial infarction, the risk of a wrong diagnosis is low. Part 2 was a placebo-controlled trial involving 100 patients in which 57 received anisoylated plasminogen streptokinase activator complex (APSAC) (30 U) at home and 43 received placebo at home. Patients receiving placebo at home were reevaluated on arrival in a coronary care unit and received APSAC (30 U) if indicated. The main results were that (1) diagnostic accuracy was good--all patients had an acute coronary syndrome and 97 of 100 patients had myocardial infarction; (2) time gain was approximately 60 minutes; (3) coronary patency rate was 72%; (4) ejection fraction was higher in the prehospital group (56.7%) than in the control group (53.4%), but the difference was not significant; (5) there was no rhythmic or bleeding complication related to the prehospital treatment; (6) 5 patients died from cardiogenic shock--2 between home and hospital and 3 in the hospital (3 received thrombolytic treatment at home and 2 received placebo at home and APSAC in the hospital); and (7) prehospital administration of APSAC did not induce a delay in arrival to the coronary care unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical experience with the percutaneous hemopump during high-risk coronary angioplasty.

The percutaneous Hemopump showed beneficial effects during coronary angioplasty in 32 high-risk patients with unloading of the left ventricle during ischemia and maintaining cardiac output with mean aortic pressures of 50 mm Hg in case of cardiac arrest (3 patients). High procedure-related morbidity (occlusion of femoral artery in 2 patients; bleeding with need of transfusion in 4 patients) and mortality (4 of 32 patients) rates demonstrate the need for a very careful selection of patients.

Effect of delayed percutaneous transluminal coronary angioplasty of occluded coronary arteries after acute myocardial infarction.

Whether angioplasty of occluded vessels after myocardial infarction may have beneficial effects on left ventricular function remains unknown. Patients with a first myocardial infarction and thrombolytic therapy who had an occluded infarct-related vessel at delayed coronary angiography were referred systematically for an elective coronary angioplasty performed between 3 and 4 weeks after the myocardial infarction. All patients underwent stress-redistribution-reinjection thallium-201 single-photon emission computed tomography for myocardial viability assessment. Prior angioplasty, a quantitative evaluation of global and regional left ventricular function, was performed. The study group consisted of 38 patients (aged 57 +/- 10 years); 18 had anterior wall infarctions and 20 inferior wall infarctions, but before angioplasty 3 had a patent artery and were excluded. Angioplasty was successful in 30 patients. At follow-up 13 patients (43%) had an occluded coronary artery. In contrast with patients with an occluded coronary artery at follow-up, those with a patent coronary artery had no left ventricular enlargement and had an improvement in both left ventricular ejection fraction (from 48 +/- 9% to 52 +/- 9.8%, p = 0.002) and regional wall motion index (delta = +0.95 SD, p <0.01). In patients with a patent vessel at follow-up, there was a positive correlation between the number of myocardial viable segments and improvement of the infarct zone wall motion (r = 0.52; p = 0.035), and the number of necrotic segments at baseline was positively correlated to the 4-month changes in end-diastolic volume indexes (r = 0.6; p = 0.04). Thus, elective revascularization of occluded coronary arteries with viable myocardium after myocardial infarction improves left ventricular function and lessens remodeling if the artery remains patent during follow-up.