Multi-center experience with intravascular lithotripsy for treatment of severe calcification during transcarotid artery revascularization for high-risk patients.

OBJECTIVE: Transcarotid artery revascularization (TCAR) offers a safe alternative to carotid endarterectomy (CEA), but severe calcification is currently considered a contraindication in carotid artery stenting. This study aims to describe the safety and effectiveness of TCAR with intravascular lithotripsy (IVL) in patients with traditionally prohibitive calcific disease. METHODS: All consecutive patients who underwent TCAR+IVL from 2018-2022 at nine institutions were identified. IVL was combined with pre-dilatation angioplasty to treat calcified vessels before stent deployment. The primary outcome was a new ipsilateral stroke within 30 days. Secondary outcomes included any new ipsilateral neurologic event (stroke/transient ischemic attack [TIA]) at 30 days, technical success, and <30% residual stenosis. RESULTS: Fifty-eight patients (62% male; mean age, 78 ± 6.6 years) underwent TCAR+IVL, with 22 (38%) for symptomatic disease. Fifty-seven patients (98%) met high-risk anatomical or physiologic criteria for CEA. Forty-seven patients had severely calcific lesions. Fourteen patients (30%) had isolated eccentric plaque, 20 patients (43%) had isolated circumferential plaque, and 13 (27%) had eccentric and circumferential calcification. Mean procedure and flow reversal times were 87 ± 27 minutes and 25 ± 14 minutes. The median number of lithotripsy pulses per case was 90 (range, 30-330), and mean contrast usage was 29 mL. No patients had electroencephalogram changes or new deficits observed intraoperatively. Technical success was achieved in 100% of cases, with 98% having <30% residual stenosis on completion angiography. One patient had an in-hospital post-procedural stroke (1.72%). Four patients total had any new ipsilateral neurologic event (stroke/TIA) within 30 days for an overall rate of 6.8%. One TIA and one stroke occurred during the index hospitalization, and two TIAs occurred after discharge. Preoperative mean stenosis in patients with any postoperative neurologic event was 93% (vs 86% in non-stroke/TIA patients; P = .32), and chronic renal insufficiency was higher in patients who had a new neurologic event (75% vs 17%; P = .005). No differences were observed in calcium, procedural, or patient characteristics between the two groups. The mean follow-up was 132 days (range, 19-520 days). Three stents developed recurrent stenosis (5%) on follow-up duplex; the remainder were patent without issue. There were no reported interventions for recurrent stenosis during the study period. CONCLUSIONS: IVL sufficiently remodels calcified carotid arteries to facilitate TCAR effectively in patients with traditionally prohibitive calcific disease. One patient (1.7%) suffered a stroke within 30 days, although four patients (6.8%) sustained any new neurological event (stroke/TIA). These results raise concerns about the risks of TCAR+IVL and whether it is an appropriate strategy for patients who could potentially undergo CEA.

In-hospital and one-year outcomes are similar for women and men following transcarotid artery revascularization in symptomatic and asymptomatic patients.

OBJECTIVE: In randomized controlled trials and retrospective series, women have higher rates of periprocedural stroke and death following carotid endarterectomy and transfemoral carotid artery stenting compared with men. We sought to compare outcomes by sex following transcarotid artery revascularization (TCAR) among patients in the Vascular Quality Initiative (VQI). METHODS: We reviewed all patients in the VQI who underwent TCAR from 2017 to 2020. We stratified the analysis by symptom status. The primary outcome was in-hospital stroke/death, and secondary outcomes were in-hospital stroke and death and 1-year stroke/death, stroke, and death. We used multivariable logistic and Cox regression models to assess the association of sex with in-hospital and 1-year outcomes after adjusting for preoperative and intraoperative characteristics. RESULTS: We identified 15,851 patients who underwent TCAR, of whom 7391 (47%) were symptomatic (2708 or 37% female) and 8460 (53%) were asymptomatic (3097 or 37% female). Women were less frequently considered anatomic high risk than men in both groups (symptomatic: 43% vs 46%; P = .004; asymptomatic: 44% vs 48%; P = .004). Among symptomatic patients, women more often had severe ≥70% stenosis (89% vs 87%; P = .02). There were no differences in in-hospital death, stroke, or stroke/death for women vs men following TCAR among symptomatic or asymptomatic patients (all P > .05). After adjusting for baseline differences between groups, female sex was not associated with in-hospital stroke/death in either symptomatic (odds ratio, 1.05; 95% confidence interval, 0.72-1.56) or asymptomatic (odds ratio, 0.93; 95% confidence interval, 0.53-1.63) patients undergoing TCAR. There were also no differences in 1-year stroke, death, or stroke/death risk for women compared with men with and without symptoms on unadjusted or adjusted analyses (P > .05). CONCLUSIONS: We found no sex differences in in-hospital or 1-year stroke/death following TCAR, regardless of symptom status. TCAR appears to be as safe of a surgical procedure for women as for men in patients with both symptomatic and asymptomatic carotid artery disease.

Risk factors and impact of postoperative hypotension after carotid artery stenting in the Vascular Quality Initiative.

OBJECTIVE: Hypotension is a frequent complication of carotid artery stenting (CAS). Although common, its occurrence is unpredictable, and association with adverse events has not been well defined. The aim of this study was to identify predictors of postoperative hypotension after CAS and the association with stroke/transient ischemic attack (TIA), major adverse cardiac events (MACEs), increased length of stay (LOS), and in-hospital mortality. METHODS: This is a retrospective analysis of all CAS procedures, including transfemoral CAS (TF-CAS) and transcarotid artery revascularization (TCAR), performed in the Vascular Quality Initiative between 2003 and 2018. The primary study end point was postoperative hypotension, defined as hypotension treated with continuous infusion of a vasoactive agent for ≥15 minutes. Secondary end points included any postoperative neurologic events (stroke/TIA), MACEs (myocardial infarction, congestive heart failure, and dysrhythmias), prolonged LOS (>1 day), and in-hospital mortality. Patients' demographics predictive of hypotension were determined by multivariable logistic regression, and a risk score was developed for correlation with outcomes. RESULTS: During the time period of study, 24,699 patients underwent CAS; 19,716 (80%) were TF-CAS, 3879 (16%) were TCAR, and 1104 (4%) were not defined. Fifty-six percent were for symptomatic disease, 75% were for a primary atherosclerotic lesion, and 72% were performed under local or regional anesthesia. Postoperative hypotension occurred in 15% of TF-CAS and 14% of TCAR patients (P = .50). Patients with hypotension (vs no hypotension) had higher rates of stroke/TIA (7.3% vs 2.6%; P < .001), MACEs (9.6% vs 2.1%; P < .001), prolonged LOS (65% vs 28%; P < .001), and in-hospital mortality (2.9% vs 0.7%; P < .001). By multivariable analysis, risk factors associated with hypotension included an atherosclerotic (vs restenotic) lesion (odds ratio, 2.2; 95% confidence interval, 2.0-2.4; P < .001), female sex (1.3 [1.2-1.4]; P < .001), positive stress test result (1.3 [1.2-1.4]; P < .001), age 70 to 79 years (1.1 [1.1-1.3]; P < .002), age >80 years (1.2 [1.1-1.4]; P < .001), history of myocardial infarction or angina (1.3 [1.2-1.4]; P < .001), and an urgent (vs elective) procedure (1.1 [1.0-1.2]; P < .01). A history of hypertension was protective (0.9 [0.8-0.9]; P < .02). A normalized risk score for hypotension was created from the multivariable model. Increasing risk scores correlated directly with rates of adverse events, including postoperative stroke/TIA, MACEs, increased LOS, and increased in-hospital mortality. CONCLUSIONS: Hypotension after CAS is associated with adverse neurologic and cardiac events as well as with prolonged LOS and in-hospital mortality. A scoring tool may be valuable in stratifying patients at risk. Interventions aimed at preventing postoperative hypotension may improve outcomes with CAS.

Presentation, surgical intervention, and long-term survival in patients with Marfan syndrome.

OBJECTIVE: Patients with Marfan syndrome (MFS) often present with acute catastrophic aortic events at a young age and have a shortened life span. This study examines the impact of presentation and demographics on late survival in patients with MFS. METHODS: Adults with confirmed MFS in our thoracic aortic center dataset were identified and statistical analysis performed to identify the incidence and predictors of aortic interventions and late mortality. RESULTS: We identified 301 patients with a MFS initial diagnosis at age 17 years (interquartile range, 4-30 years) with presentation into our thoracic aortic center at 21 years (interquartile range, 8-34 years). The average follow-up in our center was 10 ± 10 years. Clinical features were 41% male, 86% white race, coronary artery disease 28%, hypertension 40%, peripheral vascular disease 19%, and anti-impulse agent in 51% (ß-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker). Distribution of operative aortic pathology was isolated to the ascending aorta (70%) and descending aorta (8%). One hundred seventy-eight patients (59%) required primary aortic surgery (36% emergent). Primary procedures were cardiac (aortic valve/root) in nature in 94%. Seventy-four patients (42%) required multiple aortic procedures at a mean of 9.2 ± 6.9 years, involving the thoracoabdominal aorta in 65%, thoracic aorta in 37%, and abdominal aorta in 21%. Patients who required multiple aortic procedures were more likely (P < .05) to have coronary artery disease (50% vs 30%), and peripheral vascular disease (43% vs 18%). Multiple aortic procedures were also more likely (P < .05) in patients who developed de novo distal dissection (14% vs 0%), had prior dissection (47% vs 18%), or unknown MFS at the time of the initial procedure (27% vs 63%). Multivariable analysis identified prior dissection as an independent predictor of need for emergent surgery (odds ratio, 13.20; 95% confidence interval, 4.64-37.30; P < .05), as well as additional aortic surgery (odds ratio, 4.42; 95% confidence interval, 1.87-10.50; P < .05). Kaplan-Meier analysis showed similar 10-year survival with or without aortic interventions (82% with vs 89% without; P = .08). Late survival was decreased in patients undergoing emergent initial procedures (66% vs 89%; P < .01), as well as those undergoing multiple operations (74% vs 86%; P = .03). CONCLUSIONS: These data indicate that, in the modern era, the mode of presentation and need for multiple procedures have a detrimental impact on late survival. Additionally, the presence of acute or chronic dissection predicts the need for additional aortic procedures during follow-up.

Outcomes of carotid endarterectomy in the Vascular Quality Initiative based on patch type.

OBJECTIVE: The Vascular Quality Initiative (VQI) is the largest registry of vascular surgical procedures and as such is capable of distinguishing small but important differences in outcomes. The goal of this study was to determine the outcomes of carotid endarterectomy (CEA) based on patch type, including bovine pericardium, autogenous vein, polytetrafluoroethylene (PTFE), and Dacron. METHODS: All primary CEAs performed with primary repair and patching (n = 70,987) within the VQI were retrospectively analyzed. Reoperative CEA and combined CEA and coronary artery bypass were excluded. Rates of any postoperative neurologic event, return to the operating room (bleeding, neurologic event, or wound complication), and restenosis (>50% and >80%) at 1-year follow-up were primary outcomes. Rates were compared by patch type using χ2 and Bonferroni analysis. Multivariate hierarchical logistic regression models were used to predict end points of postoperative neurologic event, return to the operating room, and 1-year restenosis. RESULTS: During the period of study, 2003 to 2017, there were 70,987 CEAs entered into the VQI registry. Bovine pericardium was the patch material with the highest frequency of use (n = 51,480), followed by Dacron (n = 12,356), vein (n = 1460), and PTFE (n = 1638). Bovine pericardium, vein, and Dacron had lower rates of postoperative neurologic events compared with PTFE or primary repair. Bovine pericardium had the lowest rate of restenosis at 1 year. By multivariate analysis, bovine pericardium (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.56-0.89) and protamine use (OR, 0.74; 95% CI, 0.60-0.91) were associated with a lower incidence of return to the operating room. The use of Dacron, vein, and PTFE patches was not significantly different from the reference of primary closure. Multivariate analysis of postoperative neurologic events revealed that bovine pericardium (OR, 0.59; CI, 0.48-0.72) and Dacron (OR, 0.56; CI, 0.43-0.72) were associated with lower incidence of stroke or transient ischemic attack, whereas vein and PTFE were no different from primary closure. Bovine pericardium (OR, 0.57; CI, 0.44-0.75), Dacron (OR, 0.70; CI, 0.50-0.98), vein (OR, 0.72; CI, 0.53-0.98), and never smoking (OR, 0.87; CI, 0.78-0.96) were associated with a lower incidence of restenosis at 1 year by multivariate analysis. CONCLUSIONS: Bovine pericardium has superior outcomes both postoperatively and at 1 year compared with other patch materials. The large volume of patient data contained in the VQI makes it possible to compare outcomes that have small but meaningful differences.

Chronic Kidney Disease Class Predicts Mortality After Abdominal Aortic Aneurysm Repair in Propensity-matched Cohorts From the Medicare Population.

INTRODUCTION: Chronic kidney disease (CKD) predicts mortality after abdominal aortic aneurysm (AAA) repair. Few studies are adequately powered to stratify outcomes by CKD severity. This study assesses the effect of CKD severity on survival after AAA repair. METHODS: Patients who underwent AAA repair from 2006 to 2007 were retrospectively identified in the Medicare database and stratified by CKD class as follows: normal (CKD class 1 and 2), moderate (CKD class 3), and severe (CKD class 4 and 5). Propensity matching (30:1) by clinical factors and procedure type was performed to derive well-matched comparative cohorts. Primary outcomes were 30-day and long-term mortality; secondary outcomes included hospital length of stay and cost. RESULTS: A total of 47,715 patients were included (96.7% normal, 1.88% moderate, and 1.65% severe). Propensity matching was corrected for differences between cohorts. Thirty-day mortality was higher in moderate (5.7% vs normal 2.5%; P < 0.01) and severe (9.9% vs normal 1.8%; P < 0.01) groups. Hospital length of stay increased with CKD severity (4.4 ±â€Š3.7 days normal vs 6.5 ±â€Š4.2 days moderate CKD; P < 0.01/4.7 ±â€Š3.8 days normal vs 9.1 ±â€Š4.5 days severe CKD; P < 0.01) as did cost ($23 ±â€Š14K normal vs $25 ±â€Š16K moderate; P < 0.01 /$22 ±â€Š11K normal vs $29 ±â€Š22K severe; P < 0.01). Three-year survival favored the normal cohort (80% vs 64% moderate; log rank P < 0.01 /82% normal vs 44% severe; log rank P < 0.01). CONCLUSIONS: CKD severity is an important predictor of perioperative mortality and long-term survival after AAA repair in propensity-matched cohorts. The 5-fold increase in 30-day mortality and 44% in 3-year survival suggest that elective AAA repair is contraindicated in most severe CKD patients.

Aneurysmal degeneration of the thoracoabdominal aorta after medical management of type B aortic dissections.

BACKGROUND: Patients with uncomplicated type B aortic dissections who are managed medically are at risk of aortic aneurysmal degeneration over time. However, the effect of improvement in antihypertensive medications and stricter blood pressure control is unknown. The goal of this study was to determine the rate of aneurysmal degeneration in a contemporary cohort of patients with medically treated type B dissection. METHODS: Included were all patients with acute uncomplicated type B aortic dissection who were initially managed medically between March 1999 and March 2011 and had follow-up axial imaging studies. Maximum aortic growth was calculated by comparing the initial imaging study to the most current scan or imaging obtained just before any aortic-related intervention. An increase of ≥5 mm was the threshold considered as aortic growth. Predictors of aortic aneurysmal degeneration were determined using Cox proportional hazards models. RESULTS: We identified 200 patients (61% men) with medically managed acute type B dissections receiving multiple imaging studies. Patients were an average age of 63.4 years, and 75.5% had a history of hypertension. Mean follow-up was 5.3 years (range, 0.1-14.7 years). Mean time between the initial and final imaging studies was 3.2 years (range, 0.1-12.9 years). At 5 years, only 51% were free from aortic growth. Fifty-six patients (28%) required operative intervention (50 open, 6 endovascular repair) for aneurysmal degeneration, and the actuarial 5-year freedom from intervention was 76%. After excluding five patients (2.5%) with early rapid degeneration requiring intervention within the first 2 weeks, the mean rate of aortic growth was 12.3 mm/y for the total aortic diameter, 3.8 mm/y for the true lumen diameter, and 8.6 mm/y for the false lumen diameter. Only aortic diameter at index presentation >3.5 cm was a risk factor for future growth (odds ratio, 2.54; 95% confidence interval, 1.34-4.81; P < .01). Complete thrombosis of the false lumen was protective against growth (odds ratio, 0.19; 95% confidence interval, 0.11-0.42; P < .01). CONCLUSIONS: Although medical management of uncomplicated acute, type B aortic dissections has been the standard of care, at 5 years, a significant number of patients will require operative intervention for aneurysmal degeneration. Further studies of early intervention (eg, thoracic endovascular aortic repair) for type B aortic dissection to prevent late aneurysm formation are needed.

The natural history of medically managed acute type B aortic dissection.

OBJECTIVE: Although medical management of acute uncomplicated type B aortic dissection remains the standard of care, contemporary data regarding the natural history of medically treated patients are sparse. The goal of this study was to evaluate the natural history of patients with acute type B aortic dissection who were initially managed with medical therapy alone. METHODS: All patients with acute type B aortic dissection who were initially managed medically between March 1999 and March 2011 were included. Failure of medical therapy was defined as any death or aorta-related intervention. Early failure occurred within 15 days of presentation. Predictors of long-term outcomes were determined using backward stepwise regression. RESULTS: A total of 298 patients with medically managed acute type B dissections were identified. The cohort had an average age of 65.9 years at presentation and was 61.7% male. There were 174 (58.4%) failures including 119 deaths and 87 interventions (24 endovascular, 63 open); 57 (66%) interventions were performed for aneurysmal degeneration. There were 37 (12%) early failures including 14 deaths and 25 interventions (10 endovascular, 15 open). Aneurysmal degeneration was the indication for intervention in six patients (24%). Mean follow-up was 4.2 years (range, 0.1-14.7 years). Kaplan-Meier estimate demonstrated that freedom from intervention was 77.3% ± 2.4% at 3 years and 74.2% ± 2.5% at 6 years. There were no predictors of freedom from intervention. Kaplan-Meier estimate demonstrated that the intervention-free survival was 55.0% ± 3.0% at 3 years and 41.0% ± 3.2% at 6 years. End-stage renal disease was predictive of failure of medical treatment (hazard ratio, 2.60; confidence interval, 1.19-5.66; P = .02), and age >70 years was protective against failure (hazard ratio, 0.97; confidence interval, 0.95-0.98; P < .01). Kaplan-Meier estimate demonstrated that survival after 6 years was higher in patients who underwent interventions (76% vs 58%; P = .018). CONCLUSIONS: The majority of patients with acute type B dissection will fail medical therapy over time as evidenced by a 6-year intervention-free survival of 41%. Patients who underwent any aortic intervention had a significant survival advantage over those who were treated with medical management alone. Further study is necessary to determine who will benefit most from early intervention.

Recalcitrant peroneal artery pseudoaneurysm in a patient with Hemophilia B.

Pseudoaneurysms (PAs) of arteries in the lower extremities are uncommon. In most cases, a PA of the common femoral artery develops following percutaneous access and treatment with ultrasound guided thrombin injection achieves success rates approaching 98%. In contrast, the management of a PA of the distal leg vessels is more complex and may require additional endovascular and/or surgical treatments. We present a case of a recalcitrant PA involving the distal peroneal artery that developed following blunt trauma in a patient with Hemophilia B who failed ultrasound guided thrombin injection, para-aneurysmal saline injection and required two coil embolization procedures. Our observations suggest that Factor IX supplementation combined with aggressive coil embolization is the most effective treatment approach.

Impact of hospital volume and type on outcomes of open and endovascular repair of descending thoracic aneurysms in the United States Medicare population.

OBJECTIVE: Favorable outcomes of thoracic endovascular aortic repair (TEVAR) compared with open repair for descending thoracic aortic aneurysms (DTAs) have led to increasing TEVAR use. We evaluated the effect of case volume and hospital teaching status on clinical outcomes of intact DTA repair. METHODS: The Medicare Provider Analysis and Review (MEDPAR) data set (2004 to 2007) was queried to identify open repair or TEVAR for DTA. Hospitals were stratified by DTA volume into high volume (HV; ≥ 8 cases/y) or low volume (LV; <8 cases/y) and teaching or nonteaching. The effect of hospital variables on the primary study end point of 30-day mortality and secondary end points of 30-day complications and long-term survival after open repair and TEVAR DTA repair were studied using univariate testing, multivariable regression modeling, Kaplan-Meier survival analysis, and Cox proportional hazards regression modeling. RESULTS: We identified 763 hospitals performing 3554 open repairs and 3517 TEVARs. Overall DTA repair increased (P < .01) from 1375 in 2004 to 1987 in 2007. The proportion of hospitals performing open repair significantly decreased from 95% in 2004 to 57% in 2007 (P < .01), whereas those performing TEVAR increased (P < .01) from 24% to 76%. Overall repair type shifted from open (74% in 2004, the year before initial commercial availability of TEVAR) to TEVAR (39% open in 2007; P < .01). The fraction of open repairs at LV hospitals decreased from 56% in 2004 to 44% in 2007 (P < .01), whereas TEVAR increased from 24% in 2004 to 51% in 2007 (P < .01). Overall mortality during the study interval for open repair was 15% at LV hospitals vs 11% at HV hospitals (P < .01), whereas TEVAR mortality was similar, at 3.9% in LV vs 5.5% in HV hospitals (P = .43). LV was independently associated with increased mortality after open repair (odds ratio, 1.4; 95% confidence interval, 1.1-1.8; P < .01) but not after TEVAR. There was no independent effect of hospital teaching status on mortality or complications after open repair or TEVAR repair. CONCLUSIONS: The total number of DTA repairs has significantly increased. Operative mortality for TEVAR is independent of hospital volume and type, whereas mortality after open surgery is lower at HV hospitals, suggesting that TEVAR can be safely performed across a spectrum of hospitals, whereas open surgery should be performed only at HV hospitals.

Impact of chronic kidney disease on outcomes after abdominal aortic aneurysm repair.

OBJECTIVE: Chronic kidney disease (CKD) is associated with increased morbidity and death after open abdominal aortic aneurysm (AAA) repair (OAR). This study highlights the effect of CKD on outcomes after endovascular AAA (EVAR) and OAR in contemporary practice. METHODS: The National Surgical Quality Improvement Program (NSQIP) Participant Use File (2005-2008) was queried by Current Procedural Terminology (American Medical Association, Chicago, Ill) code to identify EVAR or OAR patients, who were grouped by CKD class as having mild (CKD class 1 or 2), moderate (CKD class 3), or severe (CKD class 4 or 5) renal disease. Propensity score analysis was performed to match OAR and EVAR patients with mild CKD with those with moderate or severe CKD. Comparative analysis of mortality and clinical outcomes was performed based on CKD strata. RESULTS: We identified 8701 patients who were treated with EVAR (n = 5811) or OAR (n = 2890) of intact AAAs. Mild, moderate, and severe CKD was present in 63%, 30%, and 7%, respectively. CKD increased (P < .01) overall mortality, with rates of 1.7% (mild), 5.3% (moderate), and 7.7% (severe) in unmatched patients undergoing EVAR or OAR. Operative mortality rates in patients with severe CKD were as high as 6.2% for EVAR and 10.3% for OAR. Severity of CKD was associated with increasing frequency of risk factors; therefore, propensity matching to control for comorbidities was performed, resulting in similar baseline clinical and demographic features of patients with mild compared with those with moderate or severe disease. In propensity-matched cohorts, moderate CKD increased the risk of 30-day mortality for EVAR (1.9% mild vs 3.2% moderate; P = .013) and OAR (3.1% mild vs 8.4% moderate; P < .0001). Moderate CKD was also associated with increased morbidity in patients treated with EVAR (8.3% mild vs 12.8% moderate; P < .0001) or OAR (25.2% mild vs 32.4% moderate; P = .001). Similarly, severe CKD increased the risk of 30-day mortality for EVAR (2.6% mild vs 5.7% severe; P = .0081) and OAR (4.1% mild vs 9.9% severe; P = .0057). Severe CKD was also associated with increased morbidity in patients treated with EVAR (10.6% mild vs 19.2% severe; P < .0001) or OAR (31.1% mild vs 39.6% severe; P = .04). CONCLUSIONS: The presence of moderate or severe CKD in patients considered for AAA repair is associated with significantly increased mortality and therefore should figure prominently in clinical decision making. The high mortality of AAA repair in patients with severe CKD is such that elective repair in such patients is not advised, except in extenuating clinical circumstances.

Remote ischemic preconditioning modulates p38 MAP kinase in rat adipocutaneous flaps.

Ischemic preconditioning has been shown to improve survival of cutaneous flaps. The authors examined the effect of remote ischemic preconditioning (RIPC) on phosphorylation of p38 MAP kinase and related the results to flap survival. Female Wistar rats had 8 x 12-cm abdominal adipocutaneous flaps raised on the medial branch of the superficial epigastric artery. Controls (Group 1) had the flap elevated and the pedicle clamped for 3 hr, then closed with a sheet of plastic between the flap and abdominal wall. Group 2 animals had RIPC by tourniquet on the contralateral hind limb before the flap was dissected. Group 3 animals mimicked Group 2 and also had an infusion of the nitric oxide blocker, N-nitro-L-arginine methyl ester (L-NAME) 5 min prior to the RIPC. Group 4 had the flap elevated prior to the RIPC. All groups except Group 1 had 10 min of RIPC with 30 min of reperfusion, then 3 hr of ischemia. Tissue samples were taken at the distal margins of the flaps before preconditioning and 30 min after preconditioning for detection of p38 MAP kinase and phosphorylated p38 MAP kinase (pp38 MAP kinase). Group 2 flaps (RIPC before flap elevation) exhibited better flap tissue survival and had well-defined phosphorylation of p38 MAP kinase 30 min post RIPC, when compared to the other groups. Pre-infusion with the nitric oxide blocker (Group 3) before RIPC blocked the survival advantage conferred by preconditioning and diminished the phosphorylation of p38 MAP kinase. Tissue from all groups showed very little phosphorylation of p38 MAP kinase following 3 hr of ischemia. Thus, increased tissue survival is correlated with elevated levels of p38 MAP kinase phosphorylation following RIPC. This effect is inhibited by blockade of nitric oxide. Modulation of the p38 MAP kinase pathway may represent a protection pathway for ischemic preconditioning.