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BACKGROUND: We report a diagnostic dilemma in a rare case of cerebral contrast retention after difficult cardiac catheterization in an elderly patient loaded with prasugrel. SUMMARY: Our case report describes a 77-year-old female with history of hypertension, diabetes, and dyslipidemia who presented to emergency department complaining of chest pain. Patient was found to have an inferior wall ST elevation myocardial infarction. The patient was loaded with aspirin and prasugrel and taken for emergent cardiac catheterization. Cardiac catheterization revealed two-vessel coronary artery disease with unsuccessful attempt of percutaneous intervention. Immediately after procedure, patient developed an episode of seizure. Emergent computed tomography scan of the brain revealed hyperdensity in the right frontoparietal region consistent with intracerebral bleed. Repeat computed tomography (24 h later) revealed substantial interval improvement of hyperdensity. Follow-up magnetic resonance imaging of the head was normal. Given the lack of magnetic resonance imaging changes, the rate of resolution on computed tomography without expected subacute changes, and the lack of neurologic findings, the initial hyperdensity seen on computed tomography of the brain was believed to be secondary to contrast leakage during cardiac catheterization as opposed to intracranial hemorrhage.

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Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality in high-risk patients undergoing percutaneous coronary intervention (PCI) or other radiocontrast procedures. Approximately 25% of all patients selected for these procedures are at risk for its development. Patients who experience this complication have higher rates of mortality, longer hospital stays and poorer long-term outcomes. The occurrence of CIN is directly related to the number of co-existing clinical risk factors. Among the many risk factors, preexisting renal impairment, advanced age, the presence of diabetes mellitus and both the volume and type of the contrast agent administered are among the most important. While the precise pathophysiological mechanisms responsible for this condition are complex and incompletely understood, experimental studies suggest that the pathogenesis involves a combination of renal ischemia and direct tubular epithelial cell toxicity. At the present time, adequate periprocedural hydration and the selection of low-osmolar and, more recently, iso-osmolar contrasts agents are the only available tools to the operator for reducing the risk of this complication. Several other modalities, such as the use of NaHCO3 and hemofiltration, also appear promising in preventing the development of this complication. This article reviews the epidemiology, pathophysiology, and consequences of CIN. It also reviews the risk factors for the development of CIN, as well as the history of the various modalities studied in its prevention.

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Antiplatelet therapy plays a pivotal role in the treatment of patients across the entire spectrum of coronary artery disease. Platelets are believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. While aspirin remains the traditional antiplatelet agent in patients with CAD, adverse vascular events continue to occur in patients on aspirin therapy. Clopidogrel is a relatively new antiplatelet agent and is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. As a member of the class of drugs known as the thienopyridines, clopidogrel irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors on its surface. The findings of a number of seminal clinical trials have expanded the indications for the use of clopidogrel in patients with coronary artery disease. When used in conjunction with aspirin, these studies have demonstrated an incremental benefit of clopidogrel above and beyond that of aspirin alone. This article reviews the data supporting the use of clopidogrel in patients with atherosclerotic heart disease, and makes recommendations for its use based on the available evidence.

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Percutaneous interventions of nonaorto ostial coronary lesions are usually complex, often requiring a combined approach of debulking and stenting, insertion of multiple guidewires and long procedure duration. Debulking with atherectomy device preserves side-branch patency by reducing plaque shift while coronary stenting minimizes vessel recoil and restenosis. We retrospectively evaluated the acute and long-term results of rotational atherectomy (group R, n = 94), coronary stenting (group S, n = 39), and combination of rotational atherectomy and stenting (group R-S, n = 59) in a total of 192 patients with nonaorto ostial lesions. The number of patients with diabetes mellitus and rest angina was significantly higher in groups S and R-S. Clinical success rates were high and procedural complication rates were low and comparable in all three groups. Despite the similar reference vessel size and preprocedure minimal lumen diameter (MLD), postprocedure MLD showed a trend toward larger lumen in groups S (3.15 +/- 0.18 mm) and R-S (3.21 +/- 0.16 mm). Group S had significantly higher incidence of side-branch narrowing (30.7%), requiring intervention (15.4%). At long-term follow-up (mean of 9 +/- 4 months), target lesion revascularization rate was significantly lower in groups R-S (11.9%) and S (15.4%) compared to group R (28.9%; P = 0.02). Our nonrandomized data suggest that stenting with or without rotational atherectomy provides the best long-term approach for the interventional treatment of nonaorto ostial coronary lesions. The clinical benefit and cost effectiveness of performing rotational atherectomy before stent implantation to reduce the incidence of side-branch closure requires further study.

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OBJECTIVES: The goal of this study was to evaluate platelet function and to preliminarily assess the clinical safety of sequential treatment with tirofiban or eptifibatide followed by abciximab in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: An increasing number of acute coronary syndrome (ACS) patients are treated early with tirofiban or eptifibatide. Some later require PCI and may benefit from switching to abciximab, for which long-term benefits have been reported. METHODS: Fifty ACS patients planned for PCI were enrolled. Twenty-five patients received tirofiban followed by abciximab. Ten patients received eptifibatide followed by abciximab. Fifteen patients received only abciximab. All patients had blood samples drawn six times during the therapeutic course. Platelet function was evaluated by ADP- and TRAP-induced aggregation, flow cytometry analysis of fibrinogen binding and the cone and plate(let) analyzer, which tests shear rate-dependent platelet activation. RESULTS: Administered after tirofiban, abciximab caused a significant further decline in platelet function, as evidenced by all methods. Administered after eptifibatide, abciximab caused a significant further reduction in platelet function, as assessed by the cone and plate(let) analyzer and fibrinogen binding methods. The platelet inhibition achieved by the combination therapy was always greater than or equal to that achieved by abciximab alone. There were no major bleeding or severe thrombocytopenia episodes. Three of the 35 combination therapy patients and one of the 15 who received abciximab alone had minor bleeding. CONCLUSIONS: This is the first in vivo study of combination intravenous platelet glycoprotein IIb/IIIa inhibitor therapy. Administration of abciximab immediately after tirofiban or eptifibatide therapy effectively inhibits platelet function and appears to be safe.

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BACKGROUND: Abciximab has been shown to reduce ischemic complications and creatine kinase-myocardial band (CK-MB) elevation of both simple and complex coronary interventions. In addition to the procedural complications, one of the important mechanisms for CK-MB elevation after rotational atherectomy is an interaction between platelets and the atheromatous debris. METHODS: This study was conducted to determine whether abciximab would limit the extent of periprocedural CK-MB release after rotational atherectomy of American Heart Association/American College of Cardiology type B(2) lesions in a double-blind, randomized, placebo-controlled manner. A total of 100 lesions in 100 patients were randomized with the primary end point being a CK-MB elevation of >16 U/L. RESULTS: Procedural success was achieved in 100% in the abciximab arm compared with 98% in the placebo group with any CK-MB elevation >16 U/L of 8% in the abciximab versus 22% in the placebo group (P =.04). The peak creatine phosphokinase level (units per liter) was 102 +/- 14 versus 153 +/- 22 (P =.05) and the peak CK-MB level was 12.8 +/- 1.8 versus 24.6 +/- 3.5 (P =.06) between the abciximab and placebo groups, respectively. Slow-flow or postprocedure chest pain occurred in 14% in the abciximab group versus 30% in the placebo group (P =.04). There was 1 Q-wave myocardial infarction in the placebo arm and 1 nonhemorrhagic stroke in the abciximab group. CONCLUSIONS: Therefore the Rota ReoPro randomized trial revealed the benefit of abciximab during rotational atherectomy in reducing procedural morbidity and CK-MB elevation, and its routine use can be justified even in moderately complex lesions undergoing rotational atherectomy.

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BACKGROUND: Tests developed to monitor glycoprotein (GP) IIb/IIIa blockade do not properly reflect platelet function in vivo and need a baseline (pretreatment) value. Because GP IIb/IIIa is essential in platelet aggregation and thrombosis under shear conditions, a flow-dependent approach to monitor its inhibition can be used. METHODS AND RESULTS: We compared a test based on flow-dependent platelet deposition, the Cone and Platelet Analyzer (CPA), with in vitro platelet aggregometry and the Rapid Platelet Function Assay (RPFA) on platelet function after GP IIb/IIIa inhibition. In vitro, increasing concentrations of abciximab (0% to 100% receptor occupancy) were tested. Ex vivo, platelet function was monitored with the CPA and with aggregometry for up to 1 week after abciximab administration. The CPA was better correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA. Only the RPFA, when expressed as a ratio over baseline (pretreatment), was comparable to the CPA. Ex vivo, the CPA, but not aggregometry, showed prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade in the first week after abciximab administration. CONCLUSIONS: Platelet function assessment by shear-induced deposition is a reliable test to monitor a wide range of GP IIb/IIIa inhibition. Its accuracy does not require a baseline reference. The effects of GP IIb/IIIa blockade on platelet function should be examined under high shear conditions.

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BACKGROUND: Both retrospective studies and prospective randomized trials have shown that beta-blockers improve survival and reduce the risk of reinfarction in patients with myocardial infarction. To evaluate whether beta-blockers exert similar protective benefits during and after coronary intervention, we studied the incidence of postprocedure creatine kinase (CK)-MB elevation in patients with or without prior beta-blocker therapy and its effect on intermediate-term ( approximately 1 year) survival. METHODS AND RESULTS: We prospectively analyzed 1675 consecutive patients undergoing coronary intervention; of these patients, 643 (38.4%) were on beta-blocker therapy before the intervention. The incidence of CK-MB elevation after coronary intervention was 13.2% in patients on beta-blocker therapy before intervention and 22.1% in patients who were not on beta-blockers (P<0.001). Patients with prior beta-blocker therapy had lower persistent/recurrent postprocedure chest pain and lower preprocedure and postprocedure heart rates and mean blood pressures compared with patients who were not on beta-blockers (P<0.001). Multiple linear regression analysis revealed prior beta-blocker therapy as the sole independent factor for lower CK-MB release after coronary intervention. During intermediate-term follow-up at 15+/-3 months, patients on beta-blocker therapy before intervention had lower mortality rates compared with those not on beta-blockers (0.78% versus 1.96%; P=0. 04), although the benefit was independent of the reduction in CK-MB release. CONCLUSIONS: Our nonrandomized, prospective analysis suggests that prior beta-blocker therapy has a cardioprotective effect in limiting CK-MB release after coronary intervention and that it is associated with a lower mortality at intermediate-term follow-up.

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The observation that platelet-platelet interaction and thrombosis are ultimately regulated by the glycoprotein (GP) IIb/IIIa receptor complex, triggered the development of agents capable of interfering with this platelet receptor complex. Several large clinical trials have demonstrated the effectiveness of this class of agents. The first of these agents to show beneficial effects after coronary interventions was the mouse/human chimeric Fab fragment antibody c7E3 (abciximab; ReoPro). This study analyzes whether the addition of heparin to the GP IIb/IIIa antagonist abciximab would enhance the antithrombotic effect. Blood drawn directly from patients on aspirin who underwent interventional procedures perfused an ex vivo perfusion chamber containing a severely injured arterial wall at local rheologic conditions of a mildly stenosed coronary artery. Blood was perfused directly from patients at baseline and following administration of heparin, abciximab, or both. The antithrombotic effects of the 3 treatments were assessed by reduction of the thrombus formation on the perfused specimens. Thrombus formation at baseline was not significantly modified by the administration of heparin (13,897 +/- 1,316 vs 11,917 +/- 1,519 microm(2)). Abciximab produced a 58% reduction in thrombus formation (11,631 +/- 861 vs 4, 925 +/- 585 microm(2); p <0.001). The addition of heparin to abciximab did not further reduce thrombus area versus abciximab alone (5,651 +/- 581 vs 4,925 +/- 585 microm(2)). Thus, our data show that abciximab dramatically decreases mural thrombus formation and that combining heparin with abciximab did not add any additional antithrombotic effect to abciximab alone.

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"Optimal" percutaneous transluminal coronary angioplasty (PTCA) may have a late restenosis rate similar to stenting. We sought to assess short- and long-term results of a provisional stenting/optimal PTCA approach compared with elective stenting in a prospective, randomized study. A total of 97 patients with discrete, de novo lesions in native coronary arteries > or =3 mm in diameter were randomized 2:1 in PTCA with prolonged perfusion balloon inflation (n = 66) versus elective stenting (n = 31). Recoil after PTCA was assessed by routine delayed angiograms (5 and 20 minutes). Cross over to stent was allowed for an inadequate result; there was no on-line quantitative angiography. An independent core angiographic laboratory assessed all results and evaluated the adequacy of the subjective interpretation. Within the PTCA arm, there were 24 (36%) crossovers to stenting (5 of 24 [21%] due to recoil), whereas 2 stents could not be delivered to the lesion and crossed over to PTCA. As assessed by quantitative angiography, baseline reference vessel diameters were similar between the PTCA and stent groups. The immediate lumen diameter achieved with PTCA was smaller than that achieved with stenting (2.18+/-0.49 vs. 2.44+/-0.38 mm, respectively, p = 0.01). There were no differences in angiographic results between elective and crossover stenting and there were no in-hospital complications in any patient. Target lesion revascularization at 8 months was 19% (n = 6) in the elective stent arm versus 21% (n = 14) in the PTCA arm, p = NS; respective rates in PTCA alone and crossed over-to-stent subsets were 23% (n = 10) versus 17% (n = 4), p = NS. Angiographic restenosis was 47% after elective stenting versus 38% after PTCA (intention to treat), p = NS. By received treatment, it was 41% (11 of 27) in the group treated with the PTCA versus 33% (5 of 15) in the crossover-to-stent arm (p = NS). Thus, provisional stenting can be safely performed in the treatment of discrete, native de novo lesions. Early recoil after PTCA cannot be reliably assessed without quantitative angiography.

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Stent implantation has become the mainstay of percutaneous revascularization for most coronary lesions; in-stent restenosis (ISR) can occur in 6%-40% of stent procedures and the subsequent response to repeat intervention can possibly be predicted by the angiographic patterns of ISR. This study evaluated the incidence and predictors of angiographic patterns of ISR and its impact on subsequent target lesion revascularization (TLR) in 100 consecutive patients having Palmaz-Schatz ISR undergoing intervention. Diffuse ISR (>/=10 mm) was observed in 78% and focal ISR (>10 mm) in 22%. Diffuse vs. focal ISR occurred earlier after stent implantation and was more common in diabetics. Angiographic predictors of diffuse ISR were stent implantation for a restenotic lesion, long lesions, smaller vessel, stenting without debulking, and high-pressure balloon inflation (>16 atm). TLR after repeat intervention was 46% for diffuse and 14% for focal ISR (P < 0.02). Rotational atherectomy resulted in lower TLR (31%) vs. PTCA or restent (64%) in diffuse ISR (P < 0.004). Therefore, diffuse ISR is more common than focal ISR, usually occurs in the setting of aggressive intimal hyperplasia, and can be predicted by clinical and angiographic variables. Also, diffuse intimal hyperplasia within a stent responds poorly to PTCA and may benefit from a more aggressive debulking strategy such as rotational atherectomy. Cathet. Cardiovasc. Intervent. 49:23-29, 2000.

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The present study was conducted to evaluate the incidence of CK-MB elevation and to identify the possible mechanisms of CK-MB release after various coronary interventional devices. We prospectively studied 1,675 consecutive patients following various coronary interventions for CK-MB elevation, from January 1997 to February 1998 and followed them for in-hospital events. CK-MB elevation was detected in 313 patients (18.7%); with 1-3 x normal in 12.8%, 3-5 x normal in 3.5%, and >5 x normal in 2.4%. CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after balloon angioplasty; P < 0.01). Among the newer nonballoon devices, rotational atherectomy alone had a lower CK-MB elevation compared to stent-alone group (16.0% vs. 20.5%; P = 0.07). On univariate analysis, due to selective use of abciximab in high-risk coronary interventions, there was higher incidence of CK-MB elevation with abciximab (24.5% vs. 15.0% without abciximab; P < 0.01). Some kind of procedural complication was observed in 49% of the CK-MB elevation group, with side-branch closure being the most frequent (22.7%). In conclusion, CK-MB elevation is common after successful coronary interventions and is higher after nonballoon devices. Cathet. Cardiovasc. Intervent. 48:123-129, 1999.

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OBJECTIVES: The study evaluated the incidence and predictors of creatine kinase-MB isoenzyme (CK-MB) elevation after successful coronary intervention using current devices, and assessed the influence on in-hospital course and midterm survival. BACKGROUND: The CK-MB elevation after coronary intervention predominantly using balloon angioplasty correlates with late cardiac events of myocardial infarction (MI) and death. Whether CK-MB elevation after nonballoon devices is associated with an adverse short and midterm prognosis is unknown. METHODS: The incidence and predictors of CK-MB elevation after coronary intervention were prospectively studied in 1,675 consecutive patients and were followed for in-hospital events and survival. RESULTS: CK-MB elevation was detected in 313 patients (18.7%), with 1-3x in 12.8%, 3-5x in 3.5% and >5x normal in 2.4% of patients. Procedural complications or electrocardiogram changes occurred in only 49% of the CK-MB-elevation cases; CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after percutaneous transluminal coronary angioplasty; p < 0.01). Predictors of CK-MB elevation on multivariate analysis were diffuse coronary disease (p = 0.02), systemic atherosclerosis (p = 0.002), stent use (p = 0.04) and absence of beta-blocker therapy (p = 0.001). Adverse in-hospital cardiac events were more frequent in patients with >5x CK-MB elevation, with no significant difference between 1-5x CK-MB elevation versus normal CK-MB group. During a mean follow-up of 13 +/- 3 months, the incidence of death in the CK-MB-elevation group was 1.6% versus 1.3% in the normal CK-MB group (p = NS). CONCLUSIONS: The CK-MB elevation after coronary intervention was observed even in the absence of discernible procedural complications and was more common in patients with diffuse atherosclerosis. In-hospital clinical events requiring prolonged monitoring were higher in >5x CK-MB-elevation patients only. Midterm survival of CK-MB-elevation patients was similar to those with normal CK-MB. Our prospective analysis shows a lack of adverse in-hospital cardiac events and suggests that early discharge of stable 1-5x normal CK-MB-elevation patients after successful coronary intervention is safe.

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BACKGROUND: Antagonists of the platelet glycoprotein IIb/IIIa decrease acute ischemic complications after percutaneous coronary interventions (PCI). Abciximab (c7E3 Fab, ReoPro) has been reported to decrease thrombin generation in vitro. We investigated in vivo the effect of abciximab therapy on thrombin generation, thrombin activity, and the activated clotting time (ACT) during PCI. METHODS: We studied 32 consecutive patients who underwent PCI for unstable coronary syndromes. Group I (n = 11) was treated with heparin plus aspirin, and group II (n = 21) was treated with heparin plus aspirin plus standard-dose abciximab, administered 5 minutes after the initial heparin bolus. Patients received a standardized heparin bolus at time 0, and arterial blood specimens for prothrombin fragment F1.2, fibrinopeptide A (FPA), and ACT were obtained from the guiding catheter at 5 minutes, 10 minutes (ACT only), 20 minutes, and at the end of the PCI. Standard-dose abciximab was administered in group II only. Each patient served as his or her own control, and the changes against the baseline were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups regarding baseline characteristics, hematocrit, and platelet count. Group I patients had higher ACT and lower F1.2 and FPA compared with group II at baseline. Subsequent measurements demonstrated a gradual decrease in FPA and F1.2 in group II; the end of procedure versus baseline changes that occurred in F1.2 were significantly different compared with group I (decrease of 0.59 +/- 0.22 nmol/L in group II vs increase of 0.22 +/- 0.3 nmol/L in group I, P =.04), and a trend in the same direction was evident for FPA changes (decrease of 1.46 +/- 1.16 ng/mL in group II vs increase of 2.25 +/- 1.58 ng/mL in group I, P =.07). The ACT response to abciximab was variable, but a 6.3% increase (+20 sec) in ACT was documented 5 minutes after abciximab bolus in group II compared with the 3.4% decrease (-10 sec) observed in group I at the same time point (P =.1). CONCLUSION: Addition of abciximab to heparin plus aspirin during PCI was associated with a significant decrease in thrombin generation and a borderline decrease in thrombin activity.

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BACKGROUND: Patients with angina after a Q-wave myocardial infarction benefit from elective revascularization, but it is not known whether asymptomatic patients, including those with a totally occluded infarct-related artery, improve after revascularization. OBJECTIVE: To determine the effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling. METHODS: We prospectively studied 31 consecutive asymptomatic patients (aged 57 +/- 2 years, 24 with anterior infarcts) after Q-wave myocardial infarction with > or = 70% stenosis of the infarct-related artery (IRA) who underwent early elective revascularization (days 4-10 after myocardial infarction). Group I consisted in patients with a totally occluded IRA (n = 10), and group II consisted in patients with a patent, though stenosed, IRA (n = 21). Resting echocardiography and low-dose dobutamine echocardiography were performed at baseline (day 3 +/- 1), and rest echocardiography was repeated after an 8-week follow-up. Significant myocardial viability was defined as > or = 2 wall segments improved (in a 16-segment model of left ventricle) versus baseline, and significant functional recovery as > or = 2 segments improved versus baseline on follow-up examination. Left ventricular end-systolic volume indices (ESVI) and end-diastolic volume indices and ejection fractions were measured by using a modified version of Simpson's rule (using apical two-chamber and four-chamber views). RESULTS: The left ventricular ESVI of patients in group I had decreased by 4.2 +/- 1.9 ml/m2, whereas for patients in group II the left ventricular ESVI had increased by 4.2 +/- 1.7 ml/m2 (P = 0.006). Similarly, the left ventricular end-diastolic volume index had decreased by 0.7 +/- 2.4 ml/m2 versus baseline at follow-up for patients in group I and increased by 7.8 +/- 2.1 ml/m2 for patients in group II (P = 0.02). The left ventricular ejection fraction increased by 7.3 +/- 3% for patients in group I and decreased by 0.4 +/- 2% for patients in group II (P = 0.04). CONCLUSION: There is less global left ventricular remodeling, a potentially deleterious process, after elective revascularization early after Q-wave myocardial infarction in asymptomatic patients who had had a totally occluded IRA before revascularization than there is in patients who had already had a patent, though stenosed, IRA before revascularization. These results suggest that restoration of patency of IRA after a Q-wave myocardial infarction is beneficial even for asymptomatic patients.

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We present our single-center experience of rotational atherectomy (RA) in the first 1,000 consecutive patients divided arbitrarily into three different time periods corresponding to significant changes in technique or equipment for RA. Period I (August 1994 to April 1995; 172 cases) is characterized by early experience, longer ablation, and frequent use of intra-aortic balloon pump; period II (May 1995 to January 1996; 254 cases) is characterized by short ablation runs (20-30 sec) and use of rotaflush; period III (February 1996 to February 1997; 574 cases) is characterized by ReoPro use, neosynephrine boluses to avoid hypotension, and rota floppy wire and flexible shaft burrs. The procedural success rate has improved and complication rates have progressively declined over these three time periods. The incidence of lesion complexity (long and type C lesions) and patients with unstable rest angina have increased over these time periods of RA. Therefore, modification in procedural techniques and equipment over time have made RA a safe technique despite its use in very complex lesion subsets.

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Microvascular surgery has emerged as an attractive area for recent advances in the field of gene therapy. The present study investigated the survival of ischemic, experimental skin flaps after treatment with the gene encoding vascular endothelial growth factor (VEGF). In 30 Sprague-Dawley rats, anterior abdominal skin flaps supplied by the epigastric artery and vein were created. Ten animals were treated with a mixture of liposomes and the cDNA encoding the 121-amino acid isoform of VEGF. Another 10 animals were treated with control plasmid DNA and liposome transfection medium; a third group of 10 animals was given physiologic saline. Each solution was injected directly into the femoral artery distal to the origin of the epigastric pedicle supplying the flap. Four days after injection, the pedicle was ligated and blood flow in the flap was approximated using dye fluorescence. Seven days later, the amount of viable tissue within the flap was measured by planimetry. After the animals were killed, specimens from both the operated and nonoperated sides of the abdomen were harvested for immunohistologic evidence of VEGF protein expression. Average dye fluorescence indices of the three groups (VEGF cDNA, control plasmid, and saline) 2 hours after pedicle ligation were 35.9, 23.9, and 53.9 percent, respectively (p < 0.05). Compared with the two control groups, flaps receiving VEGF cDNA had significantly greater tissue viability at the end of 7 days: 93.9 versus 28.1 percent for the control plasmid DNA group and 31.9 percent for the saline group (p < 0.05). Immunohistochemical staining documented increased deposition of VEGF protein in flaps that were infused with the VEGF cDNA versus saline alone (p < 0.05). The results indicated that the survival of ischemic tissues can be enhanced by administration of a cDNA encoding VEGF, a protein known to be important in the process of angiogenesis and wound healing.

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