Role of nitric oxide in the effect of blood flow on neointima formation.

PURPOSE: Neointima formation after arterial injury is inhibited by increased blood flow. The object of this study was to determine whether nitric oxide mediates the effect of increased blood flow on neointima formation. METHOD: Balloon catheter-denuded rat carotid arteries were exposed to increased blood flow or control blood flow by ligation of the contralateral carotid artery. Beginning 2 days before balloon denudation, rats were given either saline vehicle alone or the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME) at a dose of 10 mg/kg/day or 2 mg/kg/day intraperitoneally. The normalized neointima area was measured 14 days after denudation. RESULTS: Blood flow was significantly increased by ligation of the contralateral carotid artery for all drug treatments (p<0.008). In rats given saline vehicle only, normalized neointima area was significantly reduced after increased blood flow compared with control blood flow (0.33+/-0.04 compared with 0.48+/-0.03; p=0.006). Systolic blood pressure was significantly elevated by treatment with high-dose L-NAME (p=0.002 compared with vehicle), but was not altered by low-dose L-NAME (p=NS compared with vehicle). Normalized neointima area was not significantly reduced after increased carotid blood flow for rats treated with either dose of L-NAME (p=NS). CONCLUSION: The inhibition of neointima formation by increased blood flow was abolished with hypertensive and nonhypertensive doses of the nitric oxide synthase inhibitor L-NAME, which suggests that the L-NAME effects are independent of systemic hemodynamic alterations. It is concluded that flow-induced inhibition of neointima formation is mediated in part by nitric oxide.

A comparison of operative approaches and parameters predictive of success in multilevel arterial occlusive disease.

BACKGROUND: The correction of abnormal inflow alone in patients with multilevel arterial occlusive disease (MLAOD) may be inadequate to relieve limb-threatening ischemia. This study was undertaken to compare operative approaches and attempt to define preoperative parameters predictive of limb salvage in patients with MLAOD. STUDY DESIGN: The outcome after revascularization for 194 patients with limb-threatening ischemia MLAOD was assessed retrospectively. One hundred fifty-one patients initially underwent an inflow operation alone. Based on whether or not these patients required an outflow operation within one year, they were divided into two groups: group 1, no outflow operation (121 patients, 121 limbs), and group 2, outflow operation required for continued ischemic symptoms (30 patients, 30 limbs). A separate group of forty-three patients (43 limbs) underwent synchronous inflow-outflow operations, or multilevel revascularization, as their initial operative procedure (group 3). RESULTS: Perioperative complications and mortality rates did not differ between groups. Limb salvage rates were similar for groups 1 and 3, whereas in group 2, limb salvage rates were significantly reduced (p = 0.0184). Long-term limb salvage after an isolated inflow procedure was associated with lack of prior vascular reconstructions (p = 0.0002), the absence of tissue loss (p = 0.0019), and an infrageniculate angiographic runoff score of less than 6 (p = 0.054). CONCLUSIONS: In patients with limb-threatening MLAOD, synchronous inflow-outflow operations can be performed with resultant morbidity and mortality rates comparable with inflow alone. After an inflow operation, the approach of "expectant management" may ultimately compromise limb salvage if a subsequent outflow operation is required.

Long-term results of venous reconstruction after vascular trauma in civilian practice.

The natural history of venous reconstruction (VR) in terms of patency and clinical outcome after vascular trauma has not been well documented. This study consists of 32 patients who had VR performed for extremity vascular trauma and were available for long-term assessment (mean follow-up time 49 months, range 6 to 108 months). The types of repair performed were as follows: lateral venorrhaphy (simple repair) (56%), interposition grafting (22%), patch repair (12.5%), and end-to-end repair (9.5%). Seventeen patients underwent venography after the operation with documentation of repair patency in eight patients (46%) and thrombosis in nine (54%). Only two patients had significant clinical edema at follow-up examination. Noninvasive venous evaluation consisted of Doppler ultrasonography, impedance plethysmography, photoplethysmography, and color-flow duplex scanning (CFDS). The photoplethysmography-derived venous refilling time of the injured extremity was 34.9 +/- 16.2 seconds whereas that of the contralateral noninjured extremity was 36.8 +/- 16.1 seconds (p = 0.5). Based on standard criteria for CFDS, 90% of VRs were patent. Eight repairs that were patent in the early postoperative period remained patent on CFDS. Of the nine repairs with early thrombosis, eight were assessed as patent on follow-up CFDS. In conclusion, VR is a durable surgical procedure associated with minimal morbidity, good long-term patency, and preservation of venous competence. The natural history of thrombosed VRs appears to be one of thrombus absorption with recanalization.

Prostacyclin production in the area of arterial endothelial denudation.

The goal of this study was to quantify arterial prostacyclin (PGI2) synthesis and platelet aggregation in the immediate area of vessel injury. Twelve mongrel dogs whose platelets aggregated maximally to added arachidonic acid (AA) were equally divided into three groups. Controls received no drug while other dogs were treated with the platelet inhibitors aspirin (ASA) 3 mg/kg/day or BM 13.505 (BM), a thromboxane receptor antagonist, 25 mg/kg/day. After 3 days of treatment, the dogs underwent balloon catheter endothelial denudation of both carotid and femoral arteries. Blood was sampled from the first carotid artery just distal to the injury at 0, 1, 5, and 10 min after restoration of flow. Venous blood samples were also obtained at 1 and 2 weeks postoperatively. Dogs were sacrificed at 2 weeks and arterial rings from a proximal normal and a denuded region were excised and tested for PGI2 production in response to added AA. While control dogs showed no statistical change in AA-induced platelet aggregation postoperatively, there appeared to be a trend for enhanced responsiveness at 1 week. Aspirin and BM inhibited AA-induced aggregation completely in all samples at all timepoints. Levels of the stable metabolite of PGI2, 6-keto-PGF1 alpha, were determined by radioimmunoassay. In control dogs, baseline PGI2 levels were 72 +/- 17 pg/ml which increased to 479 +/- 20 pg/ml immediately after restoration of flow (P less than 0.001, Student t test) and returned to basal values in 10 min (85 +/- 5 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

A nine-year experience with crossover femoro-femoro-popliteal sequential bypass.

Multisegmental arterial occlusive disease may require a combined inflow and outflow procedure for optimal treatment of limb ischemia. Twenty-one patients with unilateral iliac artery stenosis or occlusion and ipsilateral superficial femoral artery occlusion underwent crossover femoro-femoro-popliteal sequential bypass during a 9-year period. Seventeen operations were for limb salvage. Patency rates were determined separately for each segment of the bypass. Primary patency rates for the femoro-femoral segment were 89%, 83%, and 57% at 1, 2, and 5 years, respectively. Primary patency rates for the femoro-popliteal segments were 68%, 62%, and 40% at 1, 2, and 5 years, respectively. Limb salvage rates were 100%, 90%, and 77% at 1, 2, and 5 years, respectively. This experience indicates that femoro-femoro-popliteal bypass is an effective treatment in selected patients with severe ischemia due to combined iliac artery and superficial femoral artery disease.

Hollenhorst plaques: retinal manifestations and the role of carotid endarterectomy.

The ocular examinations and hospital records of 64 patients with Hollenhorst plaques were retrospectively reviewed to document any associated visual defects and to determine if carotid endarterectomy prevented the occurrence of new plaques or symptoms. One hundred nine Hollenhorst plaques were seen in 75 eyes; 18 had multiple plaques simultaneously. Visual field defects were noted in 14 eyes, four of which corresponded to the location of Hollenhorst plaques. Twenty-eight carotid endarterectomies were performed ipsilateral to a Hollenhorst plaque: 24 patients had no symptoms; four patients developed new ipsilateral asymptomatic Hollenhorst plaques at 1 to 50 months after operation. Two late strokes occurred, one of which was ipsilateral to a new Hollenhorst plaque, during a mean follow-up of 50 months (range 8 to 102 months). Thirty-seven eyes with asymptomatic Hollenhorst plaques did not undergo ipsilateral operation. Two eyes developed new Hollenhorst plaques during a mean follow-up of 23 months (range 1 to 132 months). Eight eyes in patients with no symptoms had multiple Hollenhorst plaques, one of which was associated with a subsequent stroke. Of the 29 eyes with a single Hollenhorst plaque, one subsequently experienced an ipsilateral stroke, and another had a transient ischemic attack (1 and 3 years later, respectively). Visual field defects infrequently corresponded to locations of Hollenhorst plaques. The cerebral hemisphere ipsilateral to asymptomatic plaques had a slightly increased risk of subsequent transient ischemic attack or stroke compared to the contralateral side without Hollenhorst plaques. The number of simultaneous Hollenhorst plaques in the retinal circulation did not predict clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

On-line detection of reversible myocardial ischemic injury by measurement of myocardial electrical impedance.

The metabolic and physiological alterations associated with changes in myocardial tissue electrical resistivity during ischemia were characterized to assess the feasibility of using such resistivity as an on-line indicator of the onset of ischemic injury. Twelve anesthetized dogs underwent rapid cardiac extirpation; 5 served as untreated controls, and 7 were pretreated with metoprolol tartrate. Beta blockade was used to alter the time course of ischemic injury as demonstrated previously in studies using this experimental model. In vitro measurement of myocardial resistivity, the detection of ischemic contracture, and serial measurements of tissue adenosine triphosphate (ATP) and lactate were obtained from totally ischemic left ventricles at 37 degrees C. Myocardial resistivity began to increase significantly before onset of ischemic contracture in the untreated control group (resistivity at 42.3 +/- 3.1 minutes, contracture at 53.8 +/- 3.7 minutes; p less than 0.025) as well as the metoprolol group (resistivity at 50.7 +/- 1.5 minutes, contracture at 70.0 +/- 3.5 minutes; p less than 0.005). As expected, ischemic contracture was delayed in the beta-blocked group compared with controls (p less than 0.01). Similarly, the onset of myocardial resistivity increase was delayed in the beta-blocked group (p less than 0.025). ATP and lactate levels at the onset of myocardial resistivity increase were consistent with severe but reversible injury. Resistivity changes during ischemia correlated linearly with simultaneous ATP depletion and lactate accumulation (r = 0.88 to 0.98; p less than 0.05). Furthermore, during global ischemia studied in 3 anesthetized dogs in vivo, the onset of myocardial resistivity increase occurred after 20 minutes. Finally, 6 anesthetized dogs underwent 60 minutes of in vivo regional ischemia by coronary artery occlusion, followed by 60 minutes of reperfusion. Myocardial resistivity in the ischemic region increased immediately and steadily after coronary occlusion, followed by a rapid decrease during subsequent reperfusion. These data show that myocardial resistivity may be useful for identifying severe but still reversible ischemic injury in on-line fashion during regional and global myocardial ischemia.