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Biomedical subjects

R G Bach

Publications and source records attributed to R G Bach.

At least 19 recordsLinked to original sources

Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation and coronary artery disease.

OBJECTIVES: The purpose of the study was to assess the spectrum of coronary vasodilatory reserve values in patients with angiographically normal arteries who had atypical chest pain syndromes or remote coronary artery disease or were heart transplant recipients. BACKGROUND: The measurement of post-stenotic coronary vasodilatory reserve, now possible in a large number of patients in the cardiac catheterization laboratory, is increasingly used for decision making. Controversy exists regarding the range of normal values obtained in angiographically normal coronary arteries in patients with different clinical presentations. METHODS: Quantitative coronary arteriography was performed in 214 patients classified into three groups: 85 patients with chest pain syndromes and angiographically normal arteries (group 1); 21 patients with one normal vessel and at least one vessel with > 50% diameter lumen narrowing (group 2); and 108 heart transplant recipients (group 3). Coronary vasodilatory reserve (the ratio of maximal to basal average coronary flow velocity) was measured in 416 arteries using a 0.018-in. (0.04 cm) Doppler-tipped angioplasty guide wire. Intracoronary adenosine (8 to 18 micrograms) was used to produce maximal hyperemia. RESULTS: Coronary vasodilatory reserve was higher in angiographically normal arteries in patients with chest pain syndromes (group 1:2.80 +/- 0.6 [group mean +/- SD]) than in normal vessels in patients with remote coronary artery disease (group 2: 2.5 +/- 0.95, p = 0.04); both values were significantly higher than those in the post-stenotic segment of the diseased artery (1.8 +/- 0.6, p < 0.007). Coronary vasodilatory reserve in transplant recipients (group 3) was higher than that in the other groups (3.1 +/- 0.9, p < 0.05 vs. groups 1 and 2) as a group and for individual arteries. When stratified by vessel, coronary vasodilatory reserve was similar among the left anterior descending, left circumflex and right coronary arteries. There were no differences between coronary vasodilatory reserve values on the basis of gender for patients with coronary artery disease and transplant recipients. In group 1 (chest pain), there was a trend toward higher coronary vasodilatory reserve in men than in women (2.9 +/- 0.6 vs 2.7 +/- 0.6, p = 0.07). CONCLUSIONS: These findings identify a normal reference range for studies assessing the coronary circulation and post-stenotic coronary vasodilatory reserve in patients with and without coronary artery disease encountered in the cardiac catheterization laboratory.

Aged

Determination of angiographic (TIMI grade) blood flow by intracoronary Doppler flow velocity during acute myocardial infarction.

BACKGROUND: This study compared angiographically graded coronary blood flow with intracoronary Doppler flow velocity in patients during percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction. Different TIMI angiographic flow grades (flow grades based on results of the Thrombolysis in Myocardial Infarction trial) have been associated with different clinical results after reperfusion for acute myocardial infarction. However, intracoronary blood flow velocity has not been compared with the angiographic method of determining flow grade in patients. METHODS AND RESULTS: Coronary flow velocity (measured by use of a Doppler guidewire) during primary or rescue PTCA in 41 acute myocardial infarction patients was compared with TIMI grade and cineframes-to-opacification count. Before PTCA, 34 patients had TIMI grade 0 or 1, 5 had TIMI grade 2, and 2 had TIMI grade 3 flow in the infarct artery. Flow velocity was similar among patients with TIMI grades 0, 1, or 2 but was lower than in those with TIMI grade 3 flow (9.4 +/- 5.4 versus 16.0 +/- 5.4 cm/s for TIMI grades < or = 2 versus TIMI grade 3, respectively; P < .05). After PTCA, 1 patient had TIMI grade 1, 5 had TIMI 2, and 35 had TIMI 3 flow. Poststenotic flow velocity increased from 6.6 +/- 6.1 to 20.0 +/- 11.1 cm/s (P < .01). TIMI grade 3 flow increased to 21.8 +/- 10.9 cm/s (P < .05 versus before PTCA). Although post-PTCA flow velocity correlated with angiographic cineframes-to-opacification count (r = .45; P < .02) for TIMI grade 3, there was a large overlap with TIMI grades < or = 2 that had low flow velocity (< 20 cm/s). Nine of 11 clinical events (unstable angina and coronary artery bypass graft surgery) occurred in patients with low coronary flow velocity. CONCLUSIONS: Determination of flow velocity after reperfusion may enhance patient characterization and provide the physiological rationale for clinical variations after reperfusion therapy.

Adult

Interleukin-2 receptor-specific fusion toxin inhibits barotrauma-induced arterial atherosclerosis.

Immunocytochemical analyses of human plaques and experimental arterial lesions have implicated activated lymphocytes and monocytes in the pathogenesis of atherosclerosis, as demonstrated by the expression of interleukin-2 (IL-2) membrane receptors and major histocompatibility complex class II epitopes. The objective is to determine if targeting these cells with an IL-2 receptor-specific chimeric toxin, DAB486-IL-2, can inhibit experimental post-angioplasty vascular neointimal thickening. Twenty-two atherogenically modeled rabbits were treated in vivo with DAB486-IL-2 (0.1 mg/kg per day i.v.; n = 11) or placebo (n = 11) for 10 days following aortic balloon angioplasty (4 atm x 30 s each x 2 dilatations). In vitro 3H-leucine incorporation studies of mononuclear leukocyte and vascular smooth muscle cell protein synthesis inhibition by DAB486-IL-2 were also performed. Angioplasty sites were examined for evidence of hyperproliferative atherosclerotic narrowing by quantitative angiography and histomorphometry of neointimal cross-sectional area at baseline and 6 weeks after injury. In vitro Concanavalin-A stimulated rabbit mononuclear leukocyte protein synthesis was 50% inhibited by DAB486-IL-2 at a concentration (IC50) of 6 x 10(-11) M. Rabbit vascular smooth muscle cells were approximately 150-fold less sensitive to DAB486-IL-2 (IC50 = 10(-8) M). In vivo studies showed no change in angioplasty site angiographic minimum luminal diameter at 6 weeks in DAB486-IL-2 treated animals (from 2.96 +/- 0.52 to 2.96 +/- 0.48 mm; percent cross-sectional area reduction = 1 +/- 10%; P = N.S.). In control animals, luminal diameter decreased from 2.79 +/- 0.4 to 2.32 +/- 0.52 mm at 6 weeks, and percent cross-sectional area was reduced by 34 +/- 14% (P < 0.01 vs. placebo). Quantitative histomorphometric angioplasty segmental intimal cross-sectional area reduction of treated and placebo vessels also differed significantly (19 +/- 16% vs. 31 +/- 21%; P < 0.05). DAB486-IL-2 caused no adverse effects on animal survival, weight or hepatic transaminase levels. We conclude that post-angioplasty administration of the chimeric toxin DAB486-IL-2 inhibits angiographic narrowing and neointimal thickening in the atherogenic rabbit model. Although this IL-2 receptor-specific molecule was cytotoxic in vitro for activated mononuclear leukocytes and vascular smooth muscle cells, systemic toxicity did not occur in vivo at a dose comparable to that evaluated in clinical trials of this agent. Potential anti-proliferative effects of this chimeric toxin may be mediated by direct local inhibition of leukocyte-mediated inflammation, or through the indirect modification of vascular cell mitogenesis and cytokine release.

Angioplasty, Balloon

Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease.

The functional significance of coronary stenoses is frequently determined by adjunctive noninvasive myocardial perfusion imaging. Poststenotic coronary flow velocity and pressure can be measured directly during routine cardiac catheterization. The aim of this study was to correlate poststenotic (distal) flow velocity and pressure with stress perfusion imaging in patients. Quantitative angiography, basal and hyperemic transstenotic coronary flow velocities, and pressure gradients were measured in 50 patients within 1 week of exercise (n = 29) or of pharmacologic (n = 21) stress perfusion imaging. Twenty-two of 25 patients (88%) with reversible perfusion abnormalities had diminished distal coronary flow velocity reserves (CFVR) of < or = 2.0 x baseline, whereas 22 of 25 (88%) with normal perfusion imaging studies had a normal distal CFVR of > 2.0 (p = 0.000 1). Thirteen of 25 patients (52%) with reversible perfusion abnormalities had transstenotic gradients > or = 20 mm Hg, whereas 20 of 25 (80%) with normal perfusion studies had gradients <20 mm Hg (p = 0.01). Quantitative angiography did not differentiate patients with normal versus abnormal myocardial perfusion imaging. Distal CFVR was correlated more significantly with myocardial perfusion imaging results (kappa = 0.76) than with pressure gradients (kappa = 0.32). Exercise and pharmacologic stress myocardial perfusion imaging abnormalities reflect diminished post-stenotic coronary flow to a greater degree than transstenotic pressure gradients.

Adult

Translesional pressure and flow responses in a patient with a vasoactive and atherosclerotic coronary artery.

Sympathetic stimulation produces characteristic changes in systemic and coronary hemodynamics which can be detected by pressure and flow velocity measurements in patients with coronary artery disease. In this particular patient with a highly reactive coronary vasculature in association with a fixed obstructive lesion, marked vasoreactivity produced striking differences in the resting translesional pressure gradient and flow velocity. Intracoronary nitroglycerin was immediately effective in relieving adverse vasoconstrictor tone. Studies of coronary hemodynamics during sympathetic stimulation in such patients will lead to improved understanding of the therapeutic modalities and associated interventional techniques to treat ischemic producing vasoreactive coronary arteries.

Adult

Differential characterization of human coronary collateral blood flow velocity.

The functional importance and protective nature of the coronary collateral circulation has been well established. There are few data, however, regarding the phasic nature and absolute velocities of collateral flow in patients. The aim of this study was to characterize and quantify ipsilateral coronary collateral blood flow velocity in patients during coronary angioplasty. Coronary collateral flow velocity was measured in 49 patients during coronary angioplasty. Angiographic collateral filling was categorized by the Rentrop grading scale (0 to 3) and by anatomic pathway (epicardial, intramyocardial, or unknown [acutely recruited]). Collateral blood flow velocity was measured with a Doppler-tipped guide wire placed distal to the balloon occlusion in the collateralized vessel. Collateral flow velocity was characterized as predominantly systolic or diastolic, and phasic flow patterns were defined as biphasic (both systolic and diastolic), monophasic (only systolic or diastolic), or bidirectional (antegrade and retrograde velocity). Twenty-three (47%) patients had biphasic flow; 17 (35%) patients had monophasic flow; and 9 (18%) patients had bidirectional flow. Thirty-six (73%) of 49 patients had predominantly systolic flow signals. Epicardial collateral pathways had the highest total flow velocity integral, at 15.0 +/- 7.0 (vs intramyocardial [8.4 +/- 5.7] and acutely recruitable [5.4 +/- 2.1]; p < 0.05). There were no differences in flow velocity integrals among the Rentrop angiographic grades of collateral filling. These data establish three patterns of coronary collateral blood flow and demonstrate that the majority of collateral flow in the ipsllateral receiving vessel occurs during systole. The measurement of coronary collateral flow velocity provides a unique means to study the effects of pharmacologic or mechanical interventions on human collateral blood flow.

Adult

Influence of percutaneous transluminal coronary rotational atherectomy with adjunctive percutaneous transluminal coronary angioplasty on coronary blood flow.

The purpose of this study was to examine the influence of sequential percutaneous transluminal coronary rotational atherectomy (PTCRA) and coronary angioplasty on coronary blood flow reserve in patients. Rotational coronary atherectomy restores lumen patency by partially ablating fibrocalcific plaque, releasing microparticulate debris into the distal coronary circulation. Adjunctive balloon angioplasty is usually performed to optimize the angiographic luminal dimensions. Serial alterations in coronary physiology have not been reported. Fourteen lesions in 13 patients were treated by sequential rotational atherectomy followed by adjunctive balloon angioplasty. Poststenotic baseline coronary blood flow velocity was measured by using a Doppler flow wire (FloWire, Cardiometrics, Inc., Mountain View, Calif.), and coronary blood flow was calculated by using the distal vessel cross-sectional area obtained by quantitative coronary angiography. Data were acquired at baseline and during hyperemia (12 to 18 microg of intracoronary adenosine), before and after PTCRA, and again after balloon angioplasty. The mean stenosis decreased from 76 percent +/- 12 percent at baseline to 21 percent +/- 11 percent at the completion of the procedure (p<0.01). The minimal luminal diameter (by quantitative coronary angiography) was 0.7 +/- 0.4 mm at baseline, increased to 1.9 +/- 0.4 mm after rotational atherectomy (p<0.01), and increased to 2.4 +/- 0.5 mm after balloon angioplasty (p<0.01 versus baseline and PTCRA). Distal (poststenotic) coronary blood flow at baseline was 47 +/- 23 ml/min and 57 +/- 38 ml/min during hyperemia. After PTCRA, coronary blood flow increased to 104 +/- 59 ml/min and to 132 +/- 73 ml/min with hyperemia. After adjunctive angioplasty, coronary blood flow was 84 +/- 40 ml/min (p=not significant [NS] vs PTCRA) and increased to 143 +/- 81 ml/min with hyperemia (p=NS vs PTCRA). The poststenotic coronary flow reserve increased from an initial value of 1.1 +/- 0.2 ml/min to 1.3 +/- 0.3 ml/min after PTCRA (p=NS vs baseline) and to 1.6 +/- 0.3 ml/min after adjunctive balloon angioplasty (p<0.01 vs p=NS vs PTCRA). PTCRA significantly increased resting coronary blood flow. Adjunctive balloon angioplasty did not significantly augment resting or hyperemic coronary blood flow more than that achieved by rotational atherectomy alone. These data demonstrate that PTCRA alone improves baseline coronary blood flow with minimal additional physiologic change after adjunctive balloon angioplasty.

Aged

Influence of intimal thickening on coronary blood flow responses in orthotopic heart transplant recipients. A combined intravascular Doppler and ultrasound imaging study.

BACKGROUND: Intravascular ultrasound imaging detects epicardial intimal thickening in the majority of heart transplant recipients with angiographically normal epicardial coronary arteries. Although coronary artery vasoreactivity is abnormal after cardiac transplantation, intimal thickening does not appear to affect conduit vessel responses. However, the effect of intimal thickening on both conduit and resistance vessel responses, as measured by changes in volumetric coronary blood flow (CBF), is unknown. METHODS AND RESULTS: Epicardial coronary artery conductance and microvascular resistance vessel responses were studied after intracoronary adenosine and nitroglycerin administration in 36 orthotopic heart transplant recipients 1 month to 7 years after transplantation. Sequentially measured coronary flow average peak velocity ([APV, cm/s] 0.018 in Doppler guide wire) and epicardial luminal cross-sectional area ([CSA, mm2] 4.3F 30-MHz ultrasound catheter) data were obtained at baseline and during peak hyperemia after administration of 12 to 18 micrograms IC adenosine and 150 to 200 micrograms IC nitroglycerin. Volumetric CBF (mL/min) was calculated as CBF = APV (cm/s) x CSA (mm2) x 60 seconds/1 min x 1 cm2/100 mm2 x 0.5. Measurements were made from a discrete position in the proximal left anterior descending (LAD) artery (n = 22), mid-LAD artery (n = 7), proximal circumflex artery (n = 6), and proximal right coronary artery (n = 1). Intimal thickening was present in 19 of 32 patients (60%). Both adenosine and nitroglycerin increased APV (from 18.9 +/- 4.9 to 56.0 +/- 11.5 cm/s for adenosine and from 20.2 +/- 5.3 to 49.1 +/- 11.5 cm/s for nitroglycerin; both P < .05). Coronary flow velocity reserve was significantly higher for adenosine compared with nitroglycerin (3.1 +/- 0.6 versus 2.5 +/- 0.7, respectively; P < .001). Epicardial luminal CSA was unchanged during adenosine hyperemia compared with baseline (17.4 +/- 3.8 versus 17.3 +/- 4.0 mm2, respectively; P = NS) but was significantly greater during nitroglycerin hyperemia compared with baseline (18.7 +/- 3.8 versus 17.3 +/- 4.0 mm2, 6.2 +/- 3.6% change; P < .05). Baseline CBF was similar before drug administration. Hyperemic adenosine and nitroglycerin CBF responses (297 +/- 99 and 276 +/- 87 mL/min, respectively; P = NS) and CBF reserve (3.0 +/- 0.7 and 2.7 +/- 0.7, respectively; P = NS) were not significantly different. Importantly, intimal thickening did not diminish resting or hyperemic APV, coronary flow velocity reserve, luminal CSA, CBF, or CBF reserve responses. CONCLUSIONS: In this study of angiographically normal heart transplant recipients, epicardial intimal thickening does not diminish conduit and resistance vessel responses during endothelial-independent vasodilator administration.

Adenosine

Comparison of quantitative angiographically derived and measured translesion pressure and flow velocity in coronary artery disease.

Although quantitative coronary angiography (QCA) has been used to determine lesion severity, angiographically derived parameters of translesional physiology have not been compared with those directly measured in the same patients. Thus, the aim of this study was to correlate QCA-derived translesional pressure and flow data with directly measured data in patients. QCA (DCI-ACA program), translesional pressure gradient (2.2Fr fluid-filled tracking catheter), and intracoronary Doppler flow velocity (0.018-inch FloWire) measurements were simultaneously performed in 28 arteries (25 patients). Mean diameter stenosis was 51 +/- 2.3% (range 29 to 73). No patient had left ventricular hypertrophy or valvular heart disease. The arteries studied were left anterior descending in 14, circumflex in 8, and right coronary in 6 patients. Stenotic flow reserve and baseline and maximal gradients were calculated by the DCI program. Coronary flow reserve and baseline and maximal hyperemic gradients were also directly measured distal to the stenosis after administration of intracoronary adenosine (12 to 18 micrograms). QCA-derived pressure gradients did not correlate with the measured gradients at baseline (r2 = 0.005; p = 0.73) or at maximal hyperemia (r2 = 0.1; p = 0.13). No correlation was found between the QCA-predicted flow reserve and the coronary flow reserve measured distal to the stenosis (r2 = 0.02; p = 0.46). Furthermore, stenotic flow reserve and measured gradient were not significantly correlated (r2 = 0.1; p = 0.16). In this range of stenoses of intermediate severity, there was no correlation between the measured pressure gradient or coronary flow reserve and lesion diameter or cross-sectional area by QCA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Collateral flow velocity alterations in the supply and receiving coronary arteries during angioplasty for total coronary occlusion.

The unique observations of contralateral and ipsilateral coronary artery collateral supply before and after angioplasty suggest highly responsive conduits to hemodynamic conditions. The study of collateral supply system is not only significant for our current understanding of the dynamic behavior of the collateral circulation, but may also have important clinical implications for the treatment of patients with a chronic coronary occlusion.

Adult

Application of translesional pressure and flow velocity assessment in a severely calcified coronary narrowing in a patient with unstable angina.

While the angiographic appearance of coronary stenoses commonly directs interventional decisions, it may correlate imprecisely with hemodynamic or physiologic lesional significance. Previous data would suggest that direct measures of translesional physiology can be helpful in assessing the hemodynamic significance of stable coronary stenoses. In unstable ischemic syndromes, however, the hemodynamic severity of lesions may depend on the presence of variably occlusive intraluminal thrombus superimposed on fluctuating vessel tone. Under these circumstances, physiologic lesional assessment can yield helpful information, which nonetheless must be interpreted with caution in light of the clinical context. Determination of optimal management strategies for such patients remains difficult and must await further investigation of prognosis and outcome.

Aged