摘要:

BackgroundTransluminal extraction coronary (TEC) atherectomy is a relatively new device that has recently been approved by the Food and Drug Administration. Because of its ability to aspirate clot and atheromatous material, TEC atherectomy may be useful in patients with stenoses in saphenous vein bypass grafts.Methods and ResultsTEC atherectomy was performed on 158 saphenous vein graft lesions in 146 consecutive patients with a mean age of 65±8 years (78% men). Clinical indications for atherectomy included stable angina (37%), unstable angina (54%), and postinfarction angina after recent (<1 month) myocardial infarction (8%). Patients with acute myocardial infarction and target vessels <2 mm in diameter were excluded. The mean age of the bypass graft was 8.3±3.0 years, and 17% were diffusely diseased and degenerated. Complex lesion morphology included total occlusion (6%), eccentricity (64%), ulceration (18%), and thrombus (28%). The TEC atherectomy cutter was successfully advanced through 144 lesions (91%), but technical failures occurred in 14 lesions (9%), and these were subsequently managed by successful balloon angioplasty. Quantitative angiography revealed an increase in lumen diameter from 0.9±0.5 mm, to 1.5±0.7 mm after TEC atherectomy, to 2.3±0.8 mm after percutaneous transluminal coronary angioplasty (PTCA) (P< .001), which corresponded to decreases in diameter stenosis from 75 ± 14%, to 58±20% after TEC atherectomy, to 36±22% after PTCA (P< .001). Device success was achieved in 39.2% (post-TEC atherectomy decrease in diameter stenosis ≥20%), and procedural success was achieved in 84% (final diameter stenosis <50% in the absence of a major complication). Angiographic complications were evident in 33 lesions (20.7%) immediately after TEC atherectomy and in 8 lesions (5%) after PTCA, including distal embolization (11.9%), no-reflow (8.8%), and abrupt closure (5.0%), but no perforations. Adjunctive PTCA (and other medical therapy) successfully managed 61% of angiographic complications. Serious clinical complications included in-hospital death in 3 patients (2.0%), emergency bypass surgery in 1 patient who died (0.7%), Q wave myocardial infarction in 3 patients (2.0%), non–Q wave myocardial infarction in 4 patients (2.7%), vascular injury requiring surgical repair and/or blood transfusion in 9 patients (6.1%), and hemorrhagic cerebral infarction in 4 patients (2.7%). Using a composite clinical end point defined as in-hospital death, emergency bypass surgery, or myocardial infarction, the strongest independent correlate (P< .001) of a severe clinical complication was the development of one or more serious angiographic complications (no-reflow, distal embolization, or abrupt closure) immediately after TEC atherectomy. Complete clinical follow-up was available in 118 (92%) of 128 eligible patients at an interval of 6.0±2.5 months after discharge. Late cardiac outcome included recurrent angina treated with medical therapy (18%), repeat percutaneous intervention on the original target lesion (26%), repeat coronary artery bypass surgery (5%), Q wave myocardial infarction (4%), and late cardiac death (7%). Angiographic follow-up in 105 (80%) of 132 eligible lesions revealed a restenosis rate of 69% (defined as a diameter stenosis <50%), including 30 lesions (29%) with total occlusion of the original lesion.ConclusionsIn patients with stenoses in saphenous vein bypass grafts, TEC atherectomy is limited by the frequent need for adjunctive balloon angioplasty to achieve adequate lumen enlargement and to manage TEC atherectomy–induced complications. Although the incidence of serious clinical complications is similar to that of other percutaneous interventions in vein grafts, there is a high incidence of restenosis and late vessel occlusion. Prospective randomized studies are needed to determine the best revascularization strategy for high-risk patients with old degenerated vein grafts.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundMyocardial ouabain-binding sites and Na,KATPase activity are reduced in congestive heart failure (CHF), but the mechanisms by which CHF reduces the Na,K-ATPase remain unknown. We proposed to investigate whether the changes are accompanied by isoform-specific reductions of the Na,K-ATPase α-subunit proteins in CHF and whether similar changes could be produced by exogenous norepinephrine administration.Methods and ResultsCHF was induced in dogs by rapid ventricular pacing at a rate of 225 beats per minute for 8 weeks (protocol 1). A second group of dogs were paced at 100 beats per minute and served as controls. In protocol 2, norepinephrine was infused in normal dogs using a subcutaneous osmotic minipump for 8 weeks. The control dogs received normal saline through the pump. Animals were studied after 8 weeks of pacing or norepinephrine infusion. After the baseline hemodynamics and interstitial norepinephrine concentration had been obtained, the hearts were removed for measuring [3H]ouabain-binding sites and Na,K-ATPase α-subunit proteins using isoform-specific monoclonal antibodies.ResultsMyocardial [3H]ouabain-binding sites were reduced in dogs with CHF and chronic norepinephrine infusion. The Western blot analysis showed that adult canine hearts possess both α1and α3isoforms of the Na,K-ATPase a-subunit but not the α2isoform protein. CHF and NE infusion had no effect on the Na,K-ATPase α1-subunit protein but did reduce the α3isoform protein significantly. In addition, there was a significant inverse correlation between the amount of myocardial α3isoform protein and interstitial norepinephrine content in the dogs. In contrast, the specific activity of the sarcolemmal marker 5′-nucleotidase did not differ among the groups of animals.ConclusionsThe reduction of myocardial Na,K-ATPase in CHF is limited to the a3 isoform. Furthermore, because similar changes in myocardial ouabain-binding sites and Na,K-ATPase α3isoform were produced by chronic norepinephrine infusion, the decrease in the Na,K-ATPase in CHF is most likely mediated via excess sympathetic stimulation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundBoth vascular disease and elevated concentrations in plasma of plasminogen activator inhibitor type-1 (PAI-1) are prominent in patients with non–insulin-dependent diabetes mellitus (NIDDM). We and others have hypothesized that the increased PAI-1 may contribute to acceleration of atherosclerosis in this condition and in other states characterized by insulin resistance as well. Surprisingly, however, elevations of PAI-1 decrease when type II diabetic patients are treated with exogenous insulin, as do circulating concentrations of the precursor of insulin, proinsulin, in plasma. Accordingly, the increased PAI-1 in patients with NIDDM may reflect effects of precursors of insulin rather than or in addition to those of insulin itself. To assess this possibility directly, this study was performed to identify potential direct effects of proinsulin and proinsulin split products on synthesis of PAI-1 in liver cells, thought to be the major source of circulating PAI-1 in vivo.Methods and ResultsHep G2 cells (highly differentiated human hepatoma cells) were exposed to human proinsulin, des(31,32)proinsulin and des(64,65)proinsulin (split products of proinsulin), or C-peptide. Accumulation of PAI-1 in conditioned media increased in a time- and concentration-dependent fashion in response to the two des-intermediates [3.3-fold with des(31,32)proinsulin and 4.5-fold with des(64,65)proinsulin]. C-peptide elicited no increase. Stimulation was transduced at least in part by the insulin receptor as shown by inhibition of stimulation by insulin receptor antibodies, mediated at the level of PAI-1 gene expression as shown by the 2.2- to 2.9-fold increases in steady-state concentrations of PAI-1 mRNA, and indicative of newly synthesized protein as shown by results in metabolic labeling experiments.ConclusionsOur results are consistent with the hypothesis that precursors of insulin (proinsulin and proinsulin split products), known to be present in relatively high concentrations in plasma in patients with NIDDM and conditions characterized by insulin resistance, may directly stimulate PAI-1 synthesis, thereby attenuating fibrinolysis and accelerating atherogenesis.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundBoth plasma potassium ([K]) and epinephrine concentrations have been known to increase during exercise and decrease rapidly shortly after exercise; in addition, it is also known that exercise can promote coronary thrombosis in human and animal subjects. Many studies have shown that epinephrine has a stimulatory effect on coronary thrombosis; however, little information is available concerning the effect of raising plasma [K] on coronary thrombosis. The present study was designed to investigate the effect of raising plasma [K] and its interaction with epinephrine infusion on coronary thrombosis.Methods and ResultsA canine model of coronary thrombosis was used, and the frequency of cyclic blood flow reductions (CFRs) resulting from thrombus formation in the circumflex artery was analyzed in the study. By acutely raising plasma [K] to approximately 6.0 mEq/L, the frequency of CFRs was reduced from 8.0±0.6 to 3.7±1.0 in 40 minutes (P< .01). Epinephrine infusion (0.5 μg · kg−1. min−1) stimulated the frequency of CFRs from 7.1±0.5 to 11.5±0.7 in 40 minutes (P< .01). However, if plasma [K] was raised to approximately 6.0 mEq/L while the epinephrine infusion was continued, the frequency fell from 11.5 ±0.7 to 7.7 ± 1.1 in 40 minutes (P< .01).ConclusionsThe present study demonstrated that acutely raising plasma [K] inhibited coronary thrombosis in dogs and also blocked the potentiating effect of epinephrine on coronary thrombosis. These findings may suggest that raising plasma [K] exerts a protective effect against coronary thrombosis and that a rapid decrease in plasma [K], such as that occurring shortly after exercise, facilitates coronary artery thrombosis when the artery has a preexisting pathological condition.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundPrior in vitro and in vivo studies have reported that external ultrasound accelerates thrombolysis at intensities too low to have a direct effect on clot dissolution in the absence of a thrombolytic agent. The present study was undertaken to examine the ultrasound effect on thrombolysis and reocclusion in a rabbit thrombosis model.Methods and ResultsBlood clots were produced in a femoral artery segment with endothelial damage and distal stenosis. Recombinant tissue-type plasminogen activator (rTPA) was infused at 30 μg · kg−1· min−1for 60 minutes. Femoral artery flow was measured every 5 minutes for 2 hours. Rabbits were randomized to four groups with continuous wave ultrasound on or off with or without intravenous injection of 17 mg/kg aspirin (+US/−US/+Asp/−Asp). Ultrasound frequency and intensity were 1 MHz and 6.3 W/cm2. In seven of eight and five of five rabbits given rTPA and −US/−Asp or −US/+Asp, respectively, reflow was observed, persisting to the end of the observation period. In five of nine and four of five rabbits given rTPA and +US/−Asp or +US/+Asp, reflow was achieved, but persistent reocclusion was subsequently observed in five of five and two of four of these rabbits, respectively. Overall, femoral artery patency was worse and reocclusion occurred more often when ultrasound was added to rTPA (P= .002 by nonparametric ANOVA). However, initial reflow occurred more rapidly with ultrasound exposure (21 ± 10 and 33±6 minutes for the ±US/±Asp and ±US/−Asp groups, respectively) compared with without ultrasound (46±13 and 74±14 minutes for the −US/+Asp and −US/ −Asp groups, respectively) (P= .03 by ANOVA).ConclusionsAlthough time to initial reflow was shortened by ultrasound, it was associated with less reperfusion and more reocclusion in this model. A possible explanation for these results is ultrasound-induced platelet activation counterbalancing its thrombolysis-accelerating effect.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe development of heart failure after acute myocardial infarction (MI) may be related to alterations of left ventricular (LV) structure and function. Pathological LV remodeling may exacerbate systolic and diastolic dysfunction because increased cavity dimensions tend to increase LV wall stress. Unfortunately, many complicating factors have made it difficult to clearly define the time course of LV remodeling after myocardial infarction in patients, and the contribution of structural changes to altered function has not been fully explored.Methods and ResultsTo determine the type, magnitude, and time course of changes in LV geometry and function, we performed transthoracic Doppler echocardiographic examinations in rats before and 1 and 6 weeks after transmural MI induced by coronary ligation. LV internal diastolic dimension was greater in infarcted than in sham-operated rats at 1 and 6 weeks after MI (9.4±0.6 versus 8.0±0.5 and 10.1±0.9 versus 8.5±0.9 mm, respectively;P< .05 compared with sham-operated rats). There was significant thinning of the infarcted anterior wall at 1 and 6 weeks (0.99±0.2 versus 1.33±0.19 and 0.96±0.22 versus 1.51±0.18 mm,P< .05), while the thickness of the noninfarcted posterior wall increased but was not different from normal growth in sham-operated rats. Six weeks after surgery, fractional shortening was impaired (11±5% versus 35±5%,P< .05), and systolic thickening of the noninfarcted posterior wall was depressed (38±9% versus 67±18%,P< .05) in infarcted rats compared with shams. These changes in structure and systolic function were accompanied by progressive alterations in LV diastolic filling. Peak early filling velocity increased at 1 and 6 weeks in MI rats (91±9 versus 79±9 and 100±14 versus 74±11 cm/s,P< .05), and the deceleration rate of the early filling wave was more rapid in rats with MI (21.6±5.0 versus 15.6±3.1 and 26.1±9.8 versus 11.2±2.7 M/S2,P< .05). Late filling velocity was decreased (16±15 versus 33±7 and 15±18 versus 34±5 cm/s,P< .05), resulting in marked increase in the ratio of early to late filling. The peak velocity and the velocity-time integral of LV outflow did not change after MI.ConclusionsPostinfarction LV remodeling in the rat is characterized by progressive cavity dilatation, inadequate hypertrophy of the surviving myocardium, the gradual development of regional contractile dysfunction in noninfarcted segments, and marked abnormalities of diastolic filling. These changes can be tracked longitudinally with transthoracic echocardiography.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundPrevious studies have demonstrated that heatshock treatment results in the induction of 72-kD heat-shock protein (HSP72) and a reduction of infarct size after subsequent ischemia and reperfusion.Methods and ResultsTo test the hypothesis that the degree of protection from ischemic injury in heat-shocked rats correlates with the degree of prior HSP72 induction, rats pretreated with 40°C, 41°C, or 42°C of whole-body hyperthermia followed by 24 hours of recovery and control rats (n=6 in each group) were quantitatively assessed for the presence of myocardial HSP72 by optical densitometry of Western blots and a primary antibody that is specific for HSP72 and a tertiary antibody labeled with125I. Although rats heat-shocked to 40°C had no significant induction of myocardial HSP72, rats heat-shocked to 41°C and 42°C demonstrated progressively increased amounts of myocardial HSP72 compared with controls. Separate groups of rats heat-shocked to 40°C (n= 16), 41°C (n=37), and 42°C (n=36) with 24 hours of recovery and controls (n=26) were subjected to 35 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Compared with control and 40°C rats, there was progressive infarct size reduction, assessed by triphenyltetrazolium chloride staining, in rats that were heat-shocked to 41°C and 42°C. Furthermore, there was a direct correlation between the amount of HSP72 induced and the reduction in infarct size (r= .97,P= .037).ConclusionsThese results suggest that the improved salvage after heat-shock pretreatment may be related to the amount of HSP72 induced before prolonged ischemia and reperfusion.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe early establishment of infarct artery reperfusion by intravenous thrombolytic therapy has improved survival after acute myocardial infarction. Investigations of reperfusion have focused on the effects of specific thrombolytic agents, anticoagulation, and platelet inhibition. However, little attention has been given to the relation of arterial blood pressure to thrombolysis, a factor that probably affects thrombolytic agent delivery to the obstructing thrombus.Methods and ResultsThe effect of arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation (IABP) on reperfusion after intravenous thrombolytic therapy was studied in a canine model. A critical left anterior descending coronary artery stenosis was created by an occluder. Acute thrombosis immediately proximal to the occluder was formed by local injection of a blood and thrombin mixture into a segment of the artery that had intimal damage (groups 1 through 3). Continuous coronary blood flow velocity was measured by an epicardial Doppler probe. Group 1 (n=7) served as control. Group 2 (n=6) received an intravenous, front-loaded recombinant tissue-type plasminogen activator (rTPA) regimen (1.25 mg/kg total dose, 15% as bolus, 50% in the first 30 minutes, and 35% for the following 60 minutes). Group 3 (n=6) received the same rTPA regimen with IABP beginning at the start of rTPA administration. Coronary blood flow velocity, arterial pressure, and heart rate were observed for 150 minutes after the start of thrombolytic therapy. Five animals did not undergo coronary thrombosis (group 4) and had coronary blood flow velocity determined before and after IABP at baseline and after creation of critical stenosis. Mean systolic arterial blood pressure and heart rate were not statistically different between groups. Peak augmented diastolic pressure by IABP was 97.9±1.3% of systolic pressure in group 3 dogs. Spontaneous reperfusion did not occur in any group 1 dogs. All animals treated with rTPA reperfused. Reperfusion occurred in group 3 (13.1±2.1 minutes) earlier than in group 2 (39.2±9.4 minutes,P= .02). Overall duration of arterial patency did not differ between group 2 (81.4±16.6 minutes) and group 3 (94.9±15.3 minutes,P= .52). Reocclusions occurred with similar frequency (P= .85) in groups 2 and 3. In group 4, IABP did not increase baseline coronary blood flow velocity.ConclusionsThis study demonstrates that augmentation of diastolic arterial pressure by IABP enhances thrombolysis, leading to faster reperfusion. This effect appears to be unrelated to an increase in coronary blood flow and may be due to an effect of the augmented diastolic blood pressure wave on the obstructing thrombus. These findings suggest that the time to reperfusion by rTPA may be blood pressure dependent. The relation of arterial blood pressure to successful thrombolysis may have important implications for future treatment strategies for myocardial infarction.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundCalcitonin gene-related peptide (CGRP) is a potent dilator of epicardial conduit vessels and is released during myocardial ischemia in humans. However, the effect of CGRP on coronary arterial microvessels is still unclear, and it is unknown if CGRP modulates the tone of coronary arterial microvessels during acute myocardial ischemia.Methods and ResultsEpimyocardial microvessels were observed through a microscope equipped with a floating objective system in anesthetized open-chest dogs. Heart rate and aortic pressure were maintained at control levels. Flow velocity of the left anterior descending coronary artery (LAD) was measured with a suction-cup Doppler probe. When CGRP was cumulatively infused into the LAD (0.05, 0.5, 5.0, and 50 pmol/kg per minute) or superfused (0.03, 0.3, 3.0, and 30 nmol/L) over the left ventricular surface, arterial control microvessels < 100 μm in diameter dilated dose dependently at dosages of 0.5 to 50 pmol/kg per minute (infused) or 0.3 to 30 nmol/L (superfused), but those <100 μm dilated only at the highest dose, and those > 100 μm had greater dilation in both groups. Only the highest dose of CGRP (infused) significantly increased coronary flow. The superfusion of CGRP(8-37) (CGRP receptor antagonist, 300 nmol/L) did not affect the control diameters of coronary arterial microvessels but completely abolished CGRP-induced vasodilation at the same doses (infused and superfused). However, 300 nmol/L of CGRP(8-37) did not affect the response of coronary arterial microvessels to the LAD occlusion in any size.ConclusionsCGRP preferentially dilates the coronary arterial microvessels >100 μm in diameter but has only a small effect on those <100 μm. Endogenous CGRP does not modulate the tone of coronary arterial microvessels during acute myocardial ischemia in beating canine hearts.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAlthough epicardial coronary arteries dilate in response to changes in flow, the mechanisms responsible for this and the mechanical stimuli that are sensed by the endothelium are not completely defined. We performed the present study to determine the importance of nitric oxide in eliciting epicardial dilation to sustained changes in mean flow and pulse frequency in the coronary circulation of conscious dogs.Methods and ResultsDogs were chronically instrumented with a circumflex coronary occluder, piezoelectric crystals to measure epicardial diameter, and a coronary artery catheter placed distal to the crystals for intracoronary drug infusion. Studies were conducted in dogs in the conscious state. We inhibited nitric oxide production by administering the arginine analog Nω-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg IV), which attenuated the epicardial artery diameter changes to left atrial infusions of acetylcholine (10 μg/min) from 140±23 (±SEM) to 46±20 μm (P< .05). Epicardial dilation to sustained increases in mean coronary flow was examined by infusing adenosine into the distal coronary artery at a constant heart rate. Intracoronary adenosine increased mean flow to the same extent (180±21 versus 177±24 mL/min after L-NAME,P= NS), but inhibiting nitric oxide production had no effect on flow-mediated epicardial dilation, with coronary diameter increasing by 264±36,μm under control conditions and 294±67,μm after L-NAME (P= NS). In contrast, when pulse frequency was increased by pacing to a rate of 200 beats per minute, mean coronary flow increased to a similar level (78±9 versus 75±9 mL/min after L-NAME), but the epicardial diameter change to pacing was attenuated from 170±29 gm under control conditions to 54±23 gm after L-NAME (P< .01).ConclusionsThese results demonstrate that in vivo, nitric oxide production is primarily responsible for eliciting epicardial coronary vasodilation to endothelium-dependent agonists and changes in coronary flow pulse frequency. The failure of L-NAME to affect epicardial vasodilation during sustained increases in mean flow when pulse frequency is held constant suggests that additional mechanisms are involved in flow-mediated vasodilation of epicardial coronary arteries.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID