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Biomedical subjects

R W Smalling

Publications and source records attributed to R W Smalling.

At least 55 records · Page 3Linked to original sources

Infarct salvage with liposomal prostaglandin E1 administered by intravenous bolus immediately before reperfusion in a canine infarction-reperfusion model.

BACKGROUND: Prostaglandin E1 (PGE1) inhibits leukocyte and platelet function and reduces infarct size during left atrial infusion. Intravenous liposomal PGE1 (TLC C-53) accelerates thrombolysis and prevents reocclusion in canine coronary thrombosis. We tested the hypothesis that intravenous TLC C-53 would attenuate reperfusion injury in a canine infarction-reperfusion model. METHODS AND RESULTS: Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE1 (2 micrograms/kg), or TLC C-53 (2 micrograms/kg PGE1) after 2 hours of left anterior descending (LAD) occlusion just before reperfusion. Hemodynamic assessment, regional myocardial blood flow determination with radioactive microspheres, myocardial leukocyte infiltration by myeloperoxidase assay, and estimation of infarct size using triphenyl tetrazolium chloride staining were performed. Regional fractional shortening was measured with sonomicrometer crystals implanted in the midmyocardium. Infarct size as a percentage of the risk region was significantly reduced (P < .05) with TLC C-53 (37.9 +/- 17.4%) compared with PGE1 (56.7 +/- 13.9%) or placebo (58.0 +/- 9.9%) infusion. Infarct salvage with TLC C-53 was independent of collateral blood flow by ANCOVA. There was a dramatic reduction in myeloperoxidase activity in the infarct, risk, and border regions of dogs treated with TLC C-53 compared with placebo. Enzyme activity was also significantly reduced (P < .05) in the infarct zone with TLC C-53 (0.11 +/- 0.1 U/100 mg) treatment compared with PGE1 (0.38 +/- 0.3 U/100 mg). No significant differences in regional myocardial blood flow or myocardial function among treatment groups were identified, although there was a trend toward improved function in the TLC C-53 dogs. CONCLUSIONS: Bolus intravenous administration of TLC C-53 immediately before reperfusion results in reduced leukocyte infiltration and substantial infarct salvage. TLC C-53 mah be useful in limiting reperfusion injury during treatment of acute myocardial infarction.

Alprostadil↗

More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators.

BACKGROUND: Early restoration and maintenance of normal (TIMI 3) blood flow during acute myocardial infarction is critical for optimal preservation of left ventricular function and survival. Recombinant plasminogen activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type plasminogen activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other plasminogen activators in animal models. METHODS AND RESULTS: The RAPID Trial was designed to test the hypothesis that bolus administration of one or more dosage regimens of r-PA was superior to standard-dose alteplase (TPA) in achieving infarct-related artery patency 90 minutes after initiation of treatment. Six hundred six patients with acute myocardial infarction were randomized to one of four treatment arms: (1) TPA 100 mg i.v. over 3 hours, (2) r-PA as a 15-MU single bolus, (3) r-PA as a 10-MU bolus followed by 5 MU 30 minutes later, or (4) r-PA as a 10-MU bolus followed by 10 MU 30 minutes later. Coronary arteriography was performed at 30, 60, and 90 minutes after initiation of treatment and at hospital discharge. The 10 + 10-MU r-PA group achieved better 90-minute and 5- to 14-day TIMI 3 flow (63% [CI, 55% to 71%] versus 49% [41% to 57%], P = .019, and 88% [82% to 94%] versus 71% [63% to 79%], P < .001, respectively) than the TPA group. The TIMI 3 flow in the 10 + 10-MU r-PA group at 60 minutes was equivalent to that in the TPA group at 90 minutes (51 versus 49%). Global ejection fraction and regional wall motion in the 10 + 10-MU r-PA group were superior to those of the TPA group at hospital discharge (53 +/- 1.3% versus 49 +/- 1.3%, P = .034; -2.19 +/- 0.12 versus -2.61 +/- 0.13 SD per chord, P = .02, respectively). The 15-MU and 10 + 5-MU r-PA patency and left ventricular function results were similar to those of the TPA and inferior to those of the 10 + 10-MU r-PA group. Bleeding complications were similar between the groups. CONCLUSIONS: r-PA given as a double bolus of 10 + 10 MU achieves more rapid, complete, and sustained thrombolysis of the infarct-related artery than standard-dose TPA, without an apparent increased risk of complications. This was associated with improved global and regional left ventricular function at hospital discharge.

Coronary Angiography↗

Diffuse vasospasm following stenting of a free gastroepiploic artery graft: resolution with balloon angioplasty and intensive medical therapy.

Vasospasm following balloon angioplasty of gastroepiploic artery bypass grafts can be prevented or reversed with vasodilators. In our patient, stent deployment for ostial stenosis of a free gastroepiploic artery graft was accompanied by severe, diffuse spasm and a change in graft configuration that required both intensive medical therapy and balloon angioplasty for resolution.

Angioplasty, Balloon, Coronary↗

Successful treatment of chronic total peripheral occlusions that failed conventional techniques using the stiff backend of the Glidewire.

The vast majority of failures of transcatheter interventions in patients with peripheral vascular disease are due to inability to cross the lesion with a guidewire. Although the use of the Glidewire has clearly improved the success rate, failures with especially chronic total occlusions still occur. We describe a new technique using the very stiff backend of the Glidewire, which we have found very successful, when conventional techniques fall in crossing highly resistant lesions.

Aged↗

Coronary artery flow monitoring following coronary interventions.

Coronary guidewires with ultrasound transducer tips are commercially available and are appropriately sized for use in coronary interventions. These guidewires permit monitoring of coronary flow before, during and after the interventions. The measured flow signal contains valuable information regarding the quality and the stability of the final result. After completion of the procedure, monitoring the trend in average velocity over several minutes can reveal subtle alterations in flow that may presage abrupt closure. Abnormal or unstable flow patterns also may help predict lesions that might develop recurrences in the weeks and months after successful procedures.

Angioplasty, Balloon, Coronary↗

Coronary artery flow monitoring: the value of intravascular Doppler for detection of complications after interventions.

Ultrasound transducer-tipped guidewires can be used for coronary interventions, and they permit the monitoring of coronary flow before, during, and after the interventions. The flow signal contains valuable information regarding the quality and stability of the final result. Restoration of typical phasic flow patterns with diastolic predominance is one guide to final result. Monitoring the trend in average velocity over several minutes after completion of the procedure can detect subtle alterations in flow that may presage abrupt closure. These flow alterations might also help predict active plaques with heavy thrombus involvement that may undergo recurrence in the weeks and months after successful procedures.

Angioplasty, Balloon, Coronary↗

Transvalvular left ventricular assistance in acute myocardial infarction with cardiogenic shock and high risk angioplasty: experimental and clinical results with the Hemopump.

The Hemopump has been shown to be an effective left ventricular assist device. It is capable of supporting the circulation in patients with profound left ventricular dysfunction in the setting of cardiogenic shock. In experimental animals it seems possible that supporting the circulation immediately prior to reperfusion will produce a significant decrease in infarct size, which has important clinical ramifications, particularly in the setting of patients with large anterior myocardial infarction. The mechanism for this infarct salvage is unclear at the present time and requires further investigation, at a more basic level. The current tools available to the cardiologist include the intraaortic balloon pump and the cardiopulmonary support system (CPS), (PCs, BARD, Inc.). The Hemopump is available in Europe, but not in the United States at the present time. Clearly, the CPS system is the most powerful of the devices available, producing up to 61/m of flow. Unfortunately, there are a number of drawbacks with the CPS system, including its need for an oxygenator, which limits its useful period of support to approximately 8 hours. Additionally, support with the PCS system may be associated with adverse physiological events. The intraaortic balloon pump requires synchronization with the cardiac cycle, and hence, is not suitable for patients with significant tachyarrhythmias. Patients with overt cardiac arrest, similarly, cannot be supported with the intraaortic balloon pump. Nonetheless, the balloon pump has been associated with improved infarct salvage in an experimental animal model. On the other hand, the Hemopump, in its first version, required a surgical incision and placement of a graft onto the femoral artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Aggressive interventional treatment of acute myocardial infarction. Lessons from the animal laboratory applied to the catheterization suite.

Myocardial necrosis progresses with the duration of coronary occlusion in the early stages of acute myocardial infarction. Prompt recanalization of the infarct-related artery resulting in effective and sustained reperfusion of jeopardized myocardium is the goal of modern therapy. Clinical thrombolysis trials have demonstrated a significant survival advantage for treated patients, but only a modest recovery of global or regional systolic left ventricular function. Accelerated regimens of administering currently available thrombolytic agents are associated with early coronary patency rates approaching 85%, although effective coronary perfusion is restored in only slightly better than one half of patients treated. Primary angioplasty without antecedent thrombolytic therapy has resulted in high patency rates with superior coronary flow when performed in some experienced centers. Treatment of cardiogenic shock requires immediate mechanical or surgical intervention to reestablish coronary perfusion often following placement of a circulatory assistance device. Future trends toward very early initiation of thrombolytic therapy, improvements in adjunctive therapy and advances in the noninvasive detection of recanalization should permit selective use of aggressive interventional therapy for failed thrombolysis in a minority of patients with acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

Enhanced thrombolysis, reduced coronary reocclusion and limitation of infarct size with liposomal prostaglandin E1 in a canine thrombolysis model.

OBJECTIVES: The purpose of this study was to test the hypothesis that liposomal prostaglandin E1 (TLC C-53) would result in more rapid thrombolysis, less reocclusion and smaller infarct size when administered with heparin and streptokinase in a canine thrombolysis model. BACKGROUND: In experimental animals, prostaglandin E1 has been shown to augment thrombolysis, improve coronary flow and reduce infarct size when infused directly into the left atrium. TLC C-53 is a stable preparation of prostaglandin E1 bound by phospholipid microspheres that produces fewer adverse hemodynamic effects during intravenous use. METHODS: To investigate the effects of TLC C-53 on coronary patency and infarct salvage, we studied 30 conditioned open chest dogs. After coil-induced left anterior descending coronary artery occlusion and 1 h of clot maturation, the dogs were randomly assigned to receive a 10-min intravenous infusion of either TLC C-53 (2 micrograms/kg body weight) or placebo. Both groups then received intravenous heparin and streptokinase. Hemodynamic variables and Doppler coronary flow were monitored, and myocardial blood flow was determined using radioactive microspheres. Infarct size was assessed with triphenyltetrazolium chloride staining. RESULTS: Thrombolysis time was accelerated from 79 +/- 38 to 47 +/- 9 min (mean +/- SD), and coronary patency was greater (100% vs. 50%) with TLC C-53 than with placebo (p < 0.05). Moreover, for arteries that recanalized, coronary Doppler flow and myocardial perfusion were more severely impaired with placebo. Infarct size as a percent of the area at risk was higher (p < 0.05) with placebo (51 +/- 15%) than with TLC C-53 (33 +/- 14%). Neutrophil infiltration into ischemic myocardium determined by myeloperoxidase assay was also significantly greater in the placebo group. CONCLUSIONS: TLC C-53 administered intravenously before thrombolytic therapy resulted in a significant acceleration of thrombolysis time, improvement in coronary patency and blood flow during reperfusion and a reduction in infarct size.

Alprostadil↗

Transvalvular left ventricular assistance in cardiogenic shock secondary to acute myocardial infarction. Evidence for recovery from near fatal myocardial stunning.

OBJECTIVES: The purpose of this study was to test the hypothesis that transvalvular left ventricular assistance would support the circulation in patients with cardiogenic shock secondary to acute myocardial infarction and allow recovery of function in patients with a reversibly damaged (stunned) left ventricle. BACKGROUND: Cardiogenic shock occurs in 7.5% of patients presenting with acute myocardial infarction, resulting in survival of only 20%. Despite the use of aggressive interventional therapy in patients with shock secondary to anterior myocardial infarction, survival remains as low as 33%. METHODS: We studied 11 patients with acute myocardial infarction and cardiogenic shock, as defined by a cardiac index < 2 liters/min per m2, pulmonary capillary wedge pressure > 18 mm Hg and systolic blood pressure < 90 mm Hg during positive inotropic therapy. Patients were 57 +/- 13 years old (mean +/- SD) and had a mean left ventricular ejection fraction of 25 +/- 11%, mean arterial pressure of 69 +/- 13 mm Hg and mean cardiac index of 1.6 +/- 0.4 liters/min per m2 on admission to the study. RESULTS: During the 1st 24 h of left ventricular assistance, pulmonary capillary wedge pressure decreased from 26 +/- 4 to 16 +/- 4 mm Hg (p = 0.01), cardiac index increased from 1.6 +/- 0.4 to 2.4 +/- 0.4 liters/min per m2, and the dopamine hydrochloride dose decreased from 51 +/- 92 to 18 +/- 12 micrograms/kg body weight per min. In survivors, cardiac index improved to 3.2 +/- 0.5 liters/min per m2 (p = 0.01), and left ventricular ejection fraction improved to 34 +/- 5% (p < 0.05). The overall survival in the study group was 4 (36%) of 11 patients (95% confidence interval [CI] 8% to 65%), and 4 (66%) of 6 patients (95% CI 29% to 100%) with a Q wave anterior myocardial infarction survived. CONCLUSIONS: Transvalvular left ventricular support during cardiogenic shock complicating acute myocardial infarction is feasible and results in significant hemodynamic and functional improvement.

Female↗

Mechanical left ventricular unloading during high risk coronary angioplasty: first use of a new percutaneous transvalvular left ventricular assist device.

A new catheter mounted, transvalvular left ventricular assist device has been designed for percutaneous transfemoral access. The device, the Hemopump [14 French (Fr.) outer diameter], is based on a mixed flow rotary pump and is capable of flow rates of 1.5-2.2 l/min. The pump is inserted using a specialized 16 Fr. femoral introducer sheath. The first application of the percutaneous Hemopump in man was performed in two patients with hemodynamic compromise during high risk coronary angioplasty. In these patients, Hemopump support resulted in hemodynamic stabilization (increase in aortic pressure from 60/42 to 87/61 and from 80/60 to 100/70 mm Hg, respectively) and marked left ventricular unloading (decrease in pulmonary capillary wedge pressure from 25 to 10 and from 14 to 10 mm Hg) during balloon inflation. In both patients, percutaneous transluminal coronary angioplasty (PTCA) could be accomplished successfully. Using the system for periods of about 2 hr in each patient, we observed no vascular, hemorrhagic, or embolic complications. In both patients, only a minor increase in both plasma free hemoglobin and lactate dehydrogenase levels was noted. Our preliminary experiences suggest that the percutaneous Hemopump is safe and effective and may be a powerful alternative to other devices used for supported angioplasty.

Aged↗

Differential effects of synchronized coronary sinus retroperfusion on regional myocardial function during brief occlusion of the left anterior descending and circumflex coronary arteries.

To test the hypothesis that coronary sinus retroperfusion would preserve regional myocardial function during either left anterior descending or circumflex occlusion, sonomicrometer crystals were implanted in the midmyocardium of five chronically instrumented dogs. Regional fractional shortening was measured during 5 min of coronary occlusion with and without retroperfusion. Percent fractional shortening in the left anterior descending region fell from 18% at baseline to -4%(dyskinesis) after 3 min of left anterior descending occlusion. With coronary sinus retroperfusion, the percent fractional shortening declined from 16% at baseline to 0 (akinesis) during occlusion. A modest but significant improvement in percent fractional shortening in the ischemic region during left anterior descending occlusion occurred with retroperfusion (p < .05). By contrast, no amelioration of ischemic dysfunction occurred with retroperfusion during circumflex occlusion. Coaxial flow into the great cardiac vein during retroperfusion may provide preferential protection to ischemic myocardium supplied by the left anterior descending coronary artery. However, it is unlikely that the modest degree of improvement in regional function observed during acute left anterior descending occlusion would be mechanically important in the presence of significant ischemic dysfunction.

Animals↗

Right atrial thrombus as a complication of total parenteral nutrition in pregnancy.

BACKGROUND: Right atrial thrombus, a rare but potentially fatal complication of central venous catheter use in total parenteral nutrition, has not been reported during pregnancy. CASE: A pregnant woman with persistent hyperemesis gravidarum developed a right atrial thrombus related to central venous catheter use for total parenteral nutrition. CONCLUSION: Right atrial thrombus can be treated successfully with heparin, leading to its resolution and a normal pregnancy outcome.

Adult↗

Coronary artery flow monitoring following coronary interventions.

Technologic innovations have made it possible to measure coronary artery blood flow in awake patients. Both flow velocity as well as flow reserve can be assessed. In particular, the period of time immediately following coronary interventions offers a unique opportunity to study important features of coronary flow behavior. In 22 patients, coronary flow reserve was measured before and after an intervention, either angioplasty or atherectomy, using a 0.018-in Doppler guidewire (Flowire). The minimum lumen diameter (MLD) was increased from 1.0 +/- 0.4 to 1.7 +/- 0.4 mm, while coronary flow velocity increased significantly, rising from 29 +/- 13 to 39 +/- 14 cm/sec (p < 0.025). The maximum hyperemic velocity also increased, from 44 +/- 16 to 69 +/- 21 cm/sec. Using only the preintervention or postintervention values, the flow reserve ratio was 1.53 +/- 0.4 prior to intervention and 1.84 +/- 0.5 after intervention (p = nonsignificant). However, the post-intervention value may have been artifactually reduced by the fact that both resting as well as hyperemic velocities increased. When the post-intervention flow reserve ratio was recalculated, using the preintervention resting value, flow reserve ratio was seen in increase from 1.53 +/- 0.4 to 2.73 +/- 1.2 (p < 0.001). Measurements of coronary flow in the postintervention period also revealed several interesting phenomena. Spasm of a coronary artery was documented, and its resolution in response to intracoronary nitroglycerin was observed. Elastic recoil following angioplasty was documented by gradual decline in coronary flow over 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗