Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.

The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels.

Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs.

The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5- and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearly returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shorteining or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10 +/- 2.2 mV) at the site where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (greater than 6 h) derangement of function in the ischemic zone. Thus, brief periods of coronary occlusion result in prolonged impairement of regional myocardial function which could not have been predicted from the rapid return of the electrogram and coronary flow. These observations indicate that brief interruptions of coronary flow result either in a prolonged period of local ischemia or that alterations of mechanical induced by ischemia far outlast the repayment of the oxygen debt.

Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium?

AIM: Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca2+ handling, left ventricular (LV) contractile response during Ca2+ administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48 h of RP. METHODS: Fifty-three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow. Contractile reserve was measured with isoproterenol and intravenous (IV) Ca2+ administration. To assess the function of the sarcoplasmic reticulum (SR), post-extrasystolic potentiation (PESP) and SR Ca2+ uptake were measured. A graded treadmill test was performed in baseline and after RP (n = 14). In a separate group of animals (n = 5), myocardial performance and oxygen consumption were measured using a wide range of loading conditions. RESULTS: Left ventricular contractility was significantly decreased upon cessation of pacing. The contractile response to isoproterenol was blunted compared to a preserved response to IV Ca2+ . Post-extrasystolic potentiation was slightly increased after RP. Maximal velocity (Vmax ) of SR Ca2+ uptake was unchanged. Contractile response during exercise is attenuated after RP. External work is reduced, whereas oxygen consumption is preserved, provoking a reduced mechanical efficiency. CONCLUSION: Forty-eight-hours RP provokes a reversible LV dysfunction, while the SR function and response to exogenous Ca2+ are preserved. This is compatible with an intracellular functional remodelling to counteract Ca2+ overload provoked by RP. Left ventricular dysfunction is accompanied by a reduced contractile reserve, but an unchanged oxygen consumption, illustrating an alteration in oxygen utilization.

Effects of dobutamine on coronary stenosis physiology and morphology: comparison with intracoronary adenosine.

BACKGROUND: The mechanisms leading to dobutamine-induced ischemia are not fully understood. In the present study, we investigated the effects of high-dose intravenous dobutamine on morphological and physiological indexes of coronary stenoses. METHODS AND RESULTS: Twenty-two patients with normal left ventricular function and isolated coronary stenoses were studied. At catheterization, mean aortic pressure (P(a)), mean distal coronary pressure (P(d)), and P(d)/P(a) as an index of myocardial resistance were recorded at rest, after intracoronary adenosine, and during intravenous infusion of dobutamine (10 to 40 micrograms . kg(-1). min(-1)). Reference vessel diameter and minimal luminal diameter, as assessed by coronary angiography, did not change during dobutamine infusion compared with baseline (2.84+/-0.49 versus 2.77+/-0.41 mm and 1.35+/-0.38 versus 1. 27+/-0.31 mm, respectively; both P=NS). During peak dobutamine infusion, P(d) and P(d)/P(a) reached similar levels as during adenosine infusion (60+/-18 versus 59+/-18 mm Hg and 0.68+/-0.18 versus 0.68+/-0.17, respectively; all P=NS). In 9 patients, an additional bolus of intracoronary adenosine given at the peak dose of dobutamine failed to further decrease P(d)/P(a). Furthermore, in patients with dobutamine-induced wall motion abnormalities, the maximal decrease in P(d)/P(a) was similar during dobutamine and adenosine infusions. CONCLUSIONS: High-dose intravenous infusion of dobutamine does not modify the dimensions of the epicardial coronary stenosis. However, much like the direct coronary vasodilator adenosine, dobutamine fully exhausts myocardial resistance regardless of the presence of mechanical dysfunction.

Pressure-derived fractional flow reserve to assess serial epicardial stenoses: theoretical basis and animal validation.

Background-Fractional flow reserve (FFR) is an index of stenosis severity validated for isolated stenoses. This study develops the theoretical basis and experimentally validates equations for predicting FFR of sequential stenoses separately. Methods and Results-For 2 stenoses in series, equations were derived to predict FFR (FFR(pred)) of each stenosis separately (ie, as if the other one were removed) from arterial pressure (P(a)), pressure between the 2 stenoses (P(m)), distal coronary pressure (P(d)), and coronary occlusive pressure (P(w)). In 5 dogs with 2 stenoses of varying severity in the left circumflex coronary artery, FFR(pred) was compared with FFR(app) (ratio of the pressure just distal to that just proximal to each stenoses) and to FFR(true) (ratio of the pressures distal to proximal to each stenosis but after removal of the other one) in case of fixed distal and varying proximal stenoses (n=15) and in case of fixed proximal and varying distal stenoses (n=20). The overestimation of FFR(true) by FFR(app) was larger than that of FFR(true) by FFR(pred) (0.070+/-0.007 versus 0.029+/-0.004, P<0.01 for fixed distal stenoses, and 0.114+/-0.01 versus 0.036+/-0. 004, P<0.01 for fixed proximal stenoses). This overestimation of FFR(true) by FFR(app) was larger for fixed proximal than for fixed distal stenoses. Conclusions-The interaction between 2 stenoses is such that FFR of each lesion separately cannot be calculated by the equation for isolated stenoses (P(d)/P(a) during hyperemia) applied to each separately but can be predicted by more complete equations taking into account P(a), P(m), P(d), and P(w).

Coronary thermodilution to assess flow reserve: experimental validation.

BACKGROUND: Fractional flow reserve (FFR) and coronary flow reserve (CFR) are indices of coronary stenosis severity that provide the clinician with complementary information on the contribution of epicardial arteries and microcirculation to total resistance to myocardial blood flow. At present, FFR and CFR can only be obtained by 2 separate guidewires. The present study tested the validity of the thermodilution principle in assessing CFR with one pressure-temperature sensor-tipped guidewire. METHODS AND RESULTS: In an in vitro model, absolute flow was compared with the inverse mean transit time (1/T(mn)) of a thermodilution curve obtained after a bolus injection of 3 mL of saline at room temperature. A very close correlation (r>0.95) was found between absolute flow and 1/T(mn) when the sensor was placed >/=6 cm from the injection site. In 6 chronically instrumented dogs (60 stenoses; FFR from 0.19 to 0.98), a significant linear relation was found between flow velocity and 1/T(mn). A significant correlation was found between CFR(Doppler), which was calculated from the ratio of hyperemic to resting flow velocities, and CFR(thermo), which was calculated from the ratio of resting to hyperemic T(mn) (r=0.76; SEE=0.24; P<0.001). CONCLUSION: The present findings demonstrate the validity of the thermodilution principle to assess CFR. Because the pressure-temperature sensor was mounted in a commercially available angioplasty guidewire, this technique permits simultaneous measurements of CFR and FFR.

Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: validation in humans.

BACKGROUND: When several stenoses are present within 1 coronary artery, the hemodynamic significance of each stenosis is influenced by the presence of the other(s), and the calculation of coronary and fractional flow reserve (CFR and FFR) for each individual stenosis is confounded. Recently, we developed and experimentally validated a method to determine the true FFR of each stenosis as it would be after the removal of the other stenosis; the true FFR can be reliably predicted by coronary pressures measured before treatment at specific locations within the coronary artery using equations accounting for stenosis interaction. The aim of the present study was to test the validity of these equations in humans. METHODS AND RESULTS: In this study of 32 patients with 2 serial stenoses in 1 coronary artery, relevant pressures were measured before the intervention, after the treatment of 1 stenosis, and after the treatment of both stenoses. The true FFR of each stenosis (FFR(true)) was directly measured after the elimination of the other stenosis and compared with the value predicted (FFR(pred)) from the initial pressure measurements before treatment. Although the hyperemic gradient across 1 stenosis increased significantly (from 10+/-7 to 19+/-11 mm Hg after treatment of the other stenosis), FFR(pred) was close to FFR(true) in all patients (0.78+/-0.12 versus 0.78+/-0.11 mm Hg; r=0.92; Delta%=4+/-0%). Without accounting for stenosis interaction, the value of FFR for each stenosis would have been significantly overestimated (0.85+/-0.08; P:<0.01). CONCLUSIONS: Coronary pressure measurements made by a pressure wire at maximum hyperemia provide a simple, practical method for assessing the individual hemodynamic significance of multiple stenoses within the same artery.

Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but "Normal" coronary angiography.

BACKGROUND: Coronary arteries without focal stenosis at angiography are generally considered non-flow-limiting. However, atherosclerosis is a diffuse process that often remains invisible at angiography. Accordingly, we hypothesized that in patients with coronary artery disease, nonstenotic coronary arteries induce a decrease in pressure along their length due to diffuse coronary atherosclerosis. METHODS AND RESULTS: Coronary pressure and fractional flow reserve (FFR), as indices of coronary conductance, were obtained from 37 arteries in 10 individuals without atherosclerosis (group I) and from 106 nonstenotic arteries in 62 patients with arteriographic stenoses in another coronary artery (group II). In group I, the pressure gradient between aorta and distal coronary artery was minimal at rest (1+/-1 mm Hg) and during maximal hyperemia (3+/-3 mm Hg). Corresponding values were significantly larger in group II (5+/-4 mm Hg and 10+/-8 mm Hg, respectively; both P<0.001). The FFR was near unity (0.97+/-0.02; range, 0.92 to 1) in group I, indicating no resistance to flow in truly normal coronary arteries, but it was significantly lower (0.89+/-0.08; range, 0.69 to 1) in group II, indicating a higher resistance to flow. In 57% of arteries in group II, FFR was lower than the lowest value in group I. In 8% of arteries in group II, FFR was <0.75, the threshold for inducible ischemia. CONCLUSION: Diffuse coronary atherosclerosis without focal stenosis at angiography causes a graded, continuous pressure fall along arterial length. This resistance to flow contributes to myocardial ischemia and has consequences for decision-making during percutaneous coronary interventions.

Fractional flow reserve in patients with prior myocardial infarction.

BACKGROUND: Fractional flow reserve (FFR), an index of coronary stenosis severity, can be calculated from the ratio of hyperemic distal to proximal coronary pressure. An FFR value of 0.75 can distinguish patients with normal and abnormal noninvasive stress testing in case of normal left ventricular function. The present study aimed at investigating the value of FFR in patients with a prior myocardial infarction. Methods and Results-- In 57 patients who had sustained a myocardial infarction >/=6 days earlier, myocardial perfusion single photon emission scintigraphy (SPECT) imaging and FFR were obtained before and after angioplasty. The sensitivity and specificity of the 0.75 value of FFR to detect flow maldistribution at SPECT imaging were 82% and 87%. The concordance between the FFR and SPECT imaging was 85% (P<0.001). When only truly positive and truly negative SPECT imaging were considered, the corresponding values were 87%, 100%, and 94% (P<0.001). Patients with positive SPECT imaging before angioplasty had a significantly lower FFR than patients with negative SPECT imaging (0.52+/-0.18 versus 0.67+/-0.16, P=0.0079) but a significantly higher left ventricular ejection fraction (63+/-10% versus 52+/-10%, P=0.0009) despite a similar degree of diameter stenosis (67+/-13% versus 68+/-16%, P=NS). A significant inverse correlation was found between LVEF and FFR (R=0.29, P=0.049). CONCLUSIONS: The present data indicate (1) that the 0.75 cutoff value of FFR to distinguish patients with positive from patients with negative SPECT imaging is valid after a myocardial infarction and (2) that for a similar degree of stenosis, the value of FFR depends on the mass of viable myocardium.

Orifice variability of the stenotic aortic valve: evaluation before and after balloon aortic valvuloplasty.

The effects of balloon aortic valvuloplasty on orifice variability of the stenotic sclerocalcific aortic valve were evaluated by hemodynamic measurements of aortic valve function in 14 patients before balloon aortic valvuloplasty, during nitroprusside infusion before valvuloplasty, 48 h after valvuloplasty and during nitroprusside infusion 48 h after valvuloplasty. Aortic valve function was assessed by aortic valve area calculations with use of the Gorlin and Cannon formulas. Nitroprusside infusion before balloon aortic valvuloplasty caused no change in mean aortic valve gradient but a significant increase in mean aortic transvalvular flow from 186 +/- 46 to 202 +/- 61 ml/s (p less than 0.05), in Gorlin aortic valve area from 0.49 +/- 0.17 to 0.53 +/- 0.21 cm2 (p less than 0.05) and in Cannon aortic valve area from 0.45 +/- 0.18 to 0.49 +/- 0.22 cm2 (p less than 0.05). Nitroprusside infusion 48 h after valvuloplasty induced no change in mean aortic valve gradient but a significant increase in mean aortic transvalvular flow from 214 +/- 61 to 254 +/- 78 ml/s (p less than 0.005), in Gorlin aortic valve area from 0.71 +/- 0.25 to 0.83 +/- 0.32 cm2 (p less than 0.01) and in Cannon aortic valve area from 0.78 +/- 0.33 to 0.88 +/- 0.40 cm2 (p less than 0.05). Forty-eight hours after valvuloplasty, nitroprusside infusion induced a larger increase (40 +/- 40 ml/s) in mean transvalvular flow than before valvuloplasty (16 +/- 27 ml/s; p less than 0.05) and a larger increase (0.12 +/- 0.14 cm2) in Gorlin aortic valve area than before valvuloplasty (0.05 +/- 0.07 cm2; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative coronary angiography in predicting functional significance of stenoses in an unselected patient cohort.

OBJECTIVES: This study investigated the value of quantitative coronary angiography for predicting coronary flow reserve, as calculated from the transstenotic pressure gradient in a large, unselected patient cohort. BACKGROUND: In patients with extensive coronary artery disease, quantitative coronary angiographic findings fail to correlate with functional variables of coronary stenoses. New developments in pressure-monitoring wire technology permitted validation in humans of the concept of myocardial fractional flow reserve as assessed from coronary pressure measurements. METHODS: One hundred ten patients with normal left ventricular function were studied in the setting of coronary angioplasty. Quantitative coronary angiography was performed on-line using the ACA system. Myocardial and coronary fractional flow reserve were calculated from aortic and distal coronary pressures during maximal coronary hyperemia. RESULTS: When data before and after angioplasty were pooled, a curvilinear relation was found between myocardial fractional flow reserve and both diameter stenosis (r = 0.79) and minimal lumen diameter (r = 0.82), and a linear relation was found between myocardial fractional flow reserve and angiographic stenosis flow reserve (r = 0.78). Correlations between quantitative angiographic and pressure-derived indexes, although significant, were characterized by a large dispersion of the values of myocardial fractional flow reserve for a similar angiographic degree of stenosis. Nevertheless, the sensitivity and specificity of a minimal lumen diameter < 1.5 mm to predict myocardial fractional flow reserve < 0.72 were 96% and 89%, respectively. The corresponding values for a diameter stenosis > 50% were 93% and 85%, respectively. CONCLUSIONS: 1) In an unselected patient cohort, geometric indexes of stenosis severity derived from quantitative coronary angiography correlate significantly with physiologic variables, although these relations are imprecise in individual patients. 2) Nevertheless, the diagnostic accuracy of quantitative coronary angiography in predicting myocardial fractional flow reserve < 0.72 is high and allows its use for clinical decision making in the individual patient during diagnostic or interventional procedures.

Creatine kinase release not associated with myocardial necrosis after short periods of coronary artery occlusion in conscious baboons.

The effects of 15 minute periods of coronary artery occlusion on plasma creatine kinase (CK) and CK-MB isoenzyme activity, regional myocardial function and subsequent myocardial necrosis were studied in six conscious baboons 2 to 3 weeks after recovery from instrumentation. Mid left anterior descending coronary artery occlusion induced complete loss of systolic wall thickening (ultrasound transit time technique) and decreases in epicardial (-93%) and endocardial (-96%) blood flows (microsphere technique). Reperfusion after 15 minutes resulted in complete recovery of regional function 24 hours later. Serial plasma enzyme activity revealed a significant increase in total CK from 71 +/- 11 to 976 +/- 158 U/liter and in CK-MB from levels that were too low to measure to 21.4 +/- 2.9 U/liter. At autopsy, neither gross pathologic evidence (triphenyltetrazolium chloride staining technique) nor histologic evidence of myocardial necrosis was observed. Thus, in the conscious baboon short episodes of myocardial ischemia are associated with a significant appearance of CK and CK-MB in the blood in the absence of cellular necrosis.

Long-term follow-up after deferral of percutaneous transluminal coronary angioplasty of intermediate stenosis on the basis of coronary pressure measurement.

OBJECTIVES: This study sought to determine the safety of deferral of percutaneous transluminal coronary angioplasty (PTCA) of angiographically intermediate but functionally nonsignificant stenosis, as assessed by coronary pressure measurement and myocardial fractional flow reserve (FFRmyo). BACKGROUND: Decision making in patients with chest pain and intermediate coronary stenosis remains difficult. In these cases it is unclear whether the risk of an intervention and the potentially subsequent restenosis outweigh the future risk of an event if the lesion remains untreated. FFRmyo is a lesion-specific functional index of epicardial stenosis severity that accurately distinguishes stenoses associated with inducible ischemia. METHODS: Retrospective analysis and follow-up was performed in 100 consecutive patients referred to our centers for PTCA of an intermediate stenosis but in whom the planned intervention was deferred on the basis of an FFRmyo > or = 0.75. RESULTS: During a follow-up period of 18+/-13 months (mean +/- SD, range 3 to 42), two patients died of noncardiac causes. Ninety patients remained free of any coronary events, and their average Canadian Cardiovascular Society class decreased from 2.0+/-1.2 at baseline to 0.7+/-0.9 at follow-up (p < 0.0001). A coronary event occurred in eight patients and was target-vessel related in four. CONCLUSIONS: In patients with chest pain referred for PTCA of an intermediate stenosis, deferral of the intervention on the basis of an FFRmyo > or = 0.75 is safe and is associated with a much lower clinical event rate than if the procedure had been performed as initially planned in these patients.

Transstenotic coronary pressure gradient measurement in humans: in vitro and in vivo evaluation of a new pressure monitoring angioplasty guide wire.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Myocardial perfusion and oxygen consumption in reperfused noninfarcted dysfunctional myocardium after unstable angina: direct evidence for myocardial stunning in humans.

OBJECTIVES: To positively establish the diagnosis of myocardial stunning in patients with unstable angina and persistent wall motion abnormalities after reperfusion by coronary angioplasty. BACKGROUND: Although myocardial stunning is thought to occur in several clinical conditions, definite proof of its existence in humans is still lacking, owing to the difficulty of measuring myocardial blood flow (MBF) in absolute terms. METHODS: We studied 14 patients with unstable angina due to proximal left anterior descending coronary artery disease who presented persistent anterior wall motion abnormalities despite revascularization of the culprit lesion by percutaneous coronary angioplasty (PTCA) and who did not have clinical evidence of necrosis. Dynamic positron emission tomography (PET) with [13N]-ammonia and [11C]-acetate was performed 48 h after PTCA to determine absolute MBF and oxygen consumption (MVO2). Regional wall thickening and regional cardiac work were determined using two-dimensional echocardiography. Improvement of segmental wall motion abnormalities was followed for a median of 4 months (1.5 to 14 months). RESULTS: As judged from the changes in segmental wall motion score, regional dysfunction was spontaneously reversible in 12/14 patients and improved from 2.2 +/- 0.3 to 1.2 +/- 0.3 at late follow-up (p < 0.001). With PET, [13N]-ammonia MBF was similar among dysfunctional and remote normally contracting segments (85 +/- 29 vs. 99 +/- 20 ml x min (-1) x 100g(-1), p = not significant [n.s.]), thus demonstrating a perfusion-contraction mismatch. Despite the reduced contractile function, dysfunctional myocardium presented near normal levels of MVO2 (6.5 +/- 4.2 vs. 8.0 +/- 1.9 ml x min (-1)x 100g(-1), p = n.s.). Consequently, the regional myocardial efficiency (regional work divided by MVO2) of the dysfunctional myocardium was found to be markedly decreased as compared with normally contracting myocardium (6 +/- 6% vs. 26 +/- 6%, p < 0.001). CONCLUSIONS: This study demonstrates that human dysfunctional myocardium capable of spontaneously recovering contractile function after unstable angina endures a state of perfusion-contraction mismatch. These data for the first time provide unequivocal direct evidence for the existence of acute myocardial stunning in humans.

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results.

OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES: This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND: The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS: Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS: No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

Angiotensin II and endothelin-1 receptor antagonists have cumulative hypotensive effects in canine Page hypertension.

OBJECTIVE: To evaluate whether the cumulative hypotensive effect of the endothelin-1 receptor antagonist bosentan, previously demonstrated in the presence of an angiotensin converting enzyme inhibitor, persists under angiotensin II receptor blockade with losartan. DESIGN: The model of hypertension was canine renovascular hypertension (Page hypertension). METHODS: Ten conscious dogs, studied on two occasions, were administered losartan (a 0.1 mg/kg bolus plus 90 min infusion at 0.1 mg/kg per min) and then bosentan vehicle (experiment I) or losartan and then two cumulative doses of bosentan (a 0.3 mg/kg bolus plus 30 min infusion at 0.7 mg/kg per min; and a 3 mg/kg bolus plus 30 min infusion at 7 mg/kg per min; experiment II). RESULTS: At the end of the study, mean aortic pressure in dogs had decreased by 14% in experiment I (from 139 +/- 4.7 to 119 +/- 4.7 mmHg, P<0.05), whereas a 28% reduction occurred in experiment II (from 145 +/- 8.9 to 104 +/- 5.0 mmHg, P<0.005), corresponding to an additional 14% decrease after administration of bosentan (P<0.005 between groups). This cumulative effect of bosentan was related to a decrease in systemic vascular resistance (from 1220 +/- 119 to 847 +/- 189 mmHg/ml per min per kg x 10(3), P<0.05). Plasma angiotensin II level increased similarly in both experiments (in experiment I from 133 +/- 43 to 622 +/- 145 pg/ml, P=0.01; in experiment II from 198 +/- 63 to 771 +/- 134 pg/ml, P<0.005) whereas plasma endothelin-1 level increased only in experiment II (from 3.8 +/- 0.4 to 32.7 +/- 3.2 pg/ml, P<0.001). CONCLUSION: The cumulative hypotensive effect of bosentan suggests that, besides angiotensin II, endothelin-1 is independently involved in the pathophysiology of hypertension, which presents new therapeutic perspectives.

Delineation of myocardial viability with PET.

UNLABELLED: Relative flow and metabolic imaging (the "mismatch pattern") with PET have been proposed to identify the presence of viable myocardium in patients with ischemic left ventricular dysfunction. Yet, optimal criteria to identify dysfunctional but viable myocardium and predict significant functional improvement have not been fully defined. METHODS: Dynamic PET imaging with 13N-ammonia and 18F-deoxyglucose to assess absolute myocardial perfusion and glucose uptake was performed in 25 patients (20 men, 5 women; mean age 57 +/- 12 yr, range 30-72 yr) scheduled for coronary revascularization because of coronary artery disease, anterior wall dysfunction and mildly depressed left ventricular ejection fraction (49% +/- 11%). Global and regional left ventricular function was evaluated by contrast left ventriculography at baseline and after revascularization. RESULTS: As judged from the changes in end-systolic volume and resting anterior wall motion before and after revascularization, 17 patients with improved wall motion score and decreased end-systolic volume were considered to have viable myocardium, whereas 8 patients with either no change in regional wall motion or increased end-systolic volume were considered to have nonviable myocardium. Before revascularization, viable myocardium showed higher absolute myocardial blood flow (77 +/- 20 versus 51 +/- 9 ml (min.100 g)-1, p = 0.004) and absolute regional myocardial glucose uptake (36 +/- 14 versus 24 +/- 11 mumole (min.100 g)-1, p = 0.04) than nonviable myocardium. CONCLUSION: This study identified absolute myocardial blood flow and normalized glucose extraction as the most powerful predictors of the return of contractile function after coronary revascularization in patients with ischemic anterior wall dysfunction.

Percutaneous transluminal coronary angioplasty catheters versus fluid-filled pressure monitoring guidewires for coronary pressure measurements and correlation with quantitative coronary angiography.

The functional significance of a coronary stenosis can be assessed by measuring the translesional pressure gradient. Thirty-four patients were studied in the setting of percutaneous transluminal coronary angioplasty (PTCA) to evaluate the clinical relevance of the pressure gradient measurements by means of a PTCA balloon catheter. Both before and after PTCA, the mean pressure gradient across the stenosis was measured by means of a newly developed, 0.015-inch pressure-monitoring guidewire, first with only the wire across the stenosis (delta Pw, considered as the actual gradient), and second with the deflated balloon catheter advanced over the wire in the stenosis (delta Pb). Pressure gradients were correlated with quantitative coronary angiography of the stenotic segment. Before PTCA, mean delta Pb was larger than delta Pw (62 +/- 14 vs 30 +/- 20 mm Hg; p < 0.01). After PTCA, delta Pb remained systematically higher than delta Pw (23 +/- 14 vs 3 +/- 5 mm Hg; p < 0.01), despite a significant reduction of percent area stenosis from 84 +/- 9 to 46 +/- 17%, and an increase in minimal obstruction area from 0.98 +/- 0.48 to 3.49 +/- 1.32 mm2. A significant correlation was found between delta Pw and percent area stenosis (r2 = 0.66), with a marked increase after percent area stenosis reached 80%. The correlation between delta Pb and percent area stenosis was weaker (r2 = 0.53), the scatter of the data was larger, and the inflection point of the curve was shifted toward less severe degrees of stenosis severity.(ABSTRACT TRUNCATED AT 250 WORDS)