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Decision-making regarding level of lower extremity amputation is sometimes challenging. Selecting an appropriate anatomic level for major amputation requires consideration of tradeoffs between postoperative function and risk of wound complications that may require additional operations, including debridement and/or conversion to above-knee amputation (AKA). We evaluated the utility of common, non-invasive diagnostic tests used in clinical practice to predict the need for reoperations among patients undergoing primary, elective, below knee-amputations (BKAs) by vascular surgeons. Patients undergoing elective BKA over a 5-year period were identified using Current Procedural Terminology codes. Medical records were reviewed to characterize demographics, pre-amputation testing transcutaneous oxygen tension (TcPO 2), and ankle-brachial index (ABI). The need for ipsilateral post-BKA reoperation (including BKA revision and/or conversion to AKA) regardless of indication was the primary outcome. Associations were evaluated using univariable and multivariable logistic regression models. Cutpoints for TcPO 2 values associated with amputation reoperation were evaluated using receiver operating characteristic curves. We identified 175 BKAs, of which 46 (26.3%) required ipsilateral reoperation (18.9% BKA revisions and 14.3% conversions to AKA). The mean age was 63.3 ± 14.8 years. Most patients were male (65.1%) and White (72.0%). Mean pre-amputation calf TcPO 2 was 40.0 ± 20.5 mmHg, and mean ABI was 0.64 ± 0.45. In univariable models, post-BKA reoperation was associated with calf TcPO 2 (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P =.013) but not ABI (OR, 0.53; 95% CI, 0.19-1.46; P =.217). Univariable associations with reoperation were also identified for age (OR, 0.97; 95% CI, 0.94-0.990; P =.003) and diabetes (OR, 0.43; 95% CI, 0.21-0.87; P =.019). No associations with amputation revision were identified for gender, race, end-stage renal disease, or preoperative antibiotics. Calf TcPO 2 remained associated with post-BKA reoperation in a multivariable model (OR, 0.97; 95% CI, 0.94-0.99; P =.022) adjusted for age (OR, 0.98; 95% CI, 0.94-1.01; P =.222) and diabetes (OR, 0.98; 95% CI, 0.94-1.01; P =.559). Receiver operating characteristic analysis suggested a TcPO 2 ≥38 mmHg as an appropriate cut-point for assessing risk for BKA revision (area under the curve = 0.682; negative predictive value, 0.91). Reoperation after BKA is common, and reoperation risk was associated with pre-amputation TcPO 2. For patients undergoing elective BKA, higher risk of reoperation should be discussed with patients with an ipsilateral TcPO 2 <38 mmHg. [ABSTRACT FROM AUTHOR]

Aims Coronary microvascular smooth muscle cells (SMCs) respond to luminal pressure by developing myogenic tone (MT), a process integral to the regulation of microvascular perfusion. The cellular mechanisms underlying poor myogenic reactivity in patients with heart valve disease are unknown and form the focus of this study. Methods and results Intramyocardial coronary micro-arteries (IMCAs) isolated from human and pig right atrial (RA) appendage and left ventricular (LV) biopsies were studied using pressure myography combined with confocal microscopy. All RA- and LV-IMCAs from organ donors and pigs developed circa 25% MT. In contrast, 44% of human RA-IMCAs from 88 patients with heart valve disease had poor (<10%) MT yet retained cell viability and an ability to raise cytoplasmic Ca2+ in response to vasoconstrictor agents. Comparing across human heart chambers and species, we found that based on patient medical history and six tests, the strongest predictor of poor MT in IMCAs was increased expression of the synthetic marker caldesmon relative to the contractile marker SM-myosin heavy chain. In addition, high resolution imaging revealed a distinct layer of longitudinally aligned SMCs between ECs and radial SMCs, and we show poor MT was associated with disruptions in these cellular alignments. Conclusion These data demonstrate the first use of atrial and ventricular biopsies from patients and pigs to reveal that impaired coronary MT reflects a switch of viable SMCs towards a synthetic phenotype, rather than a loss of SMC viability. These arteries represent a model for further studies of coronary microvascular contractile dysfunction. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle contraction is suppressed by feedback dilation mediated by the endothelium. In skeletal muscle arterioles, this feedback can be activated by Ca2+ signals passing from smooth muscle through gap junctions to endothelial cells, which protrude through holes in the internal elastic lamina to make contact with vascular smooth muscle cells. Although hypothetically either Ca2+ or inositol trisphosphate (IP3) may provide the intercellular signal, it is generally thought that IP3 diffusion is responsible. We provide evidence that Ca2+ entry through L-type voltage-dependent Ca2+ channels (VDCCs) in vascular smooth muscle can pass to the endothelium through positions aligned with holes in the internal elastic lamina in amounts sufficient to activate endothelial cell Ca2+ signaling. In endothelial cells in which IP3 receptors (IP3Rs) were blocked, VDCC-driven Ca2+ events were transient and localized to the endothelium that protrudes through the internal elastic lamina to contact vascular smooth muscle cells. In endothelial cells in which IP3Rs were not blocked, VDCC-driven Ca2+ events in endothelial cells were amplified to form propagating waves. These waves activated voltage-insensitive, intermediate-conductance, Ca2+-activated K+ (IKCa) channels, thereby providing feedback that effectively suppressed vasoconstriction and enabled cycles of constriction and dilation called vasomotion. Thus, agonists that stimulate vascular smooth muscle depolarization provide Ca2+ to endothelial cells to activate a feedback circuit that protects tissue blood flow. [ABSTRACT FROM AUTHOR]

First-line treatment of peripheral artery disease (PAD) involves medical therapy and lifestyle modification. Multiple professional organizations such as the Society for Vascular Surgery and the American Heart Association/American College of Cardiology make Class I recommendations for medical management including antiplatelet, statin, antihypertensive, and cilostazol medications, as well as lifestyle therapy including exercise and smoking cessation. Although evidence supports up-front medical and lifestyle management prior to surgical intervention, it is unclear how well this occurs in contemporary clinical practice. It is also unclear whether variability in first-line treatment prior to revascularization is associated with postoperative outcomes. This study examined the proportion of patients with claudication actively receiving evidence-based therapy prior to surgery in a statewide surgical registry. We conducted a retrospective cohort study of adult patients undergoing elective open lower extremity bypass for claudication from 2012 to 2021 within a statewide surgical quality registry. The primary exposure was optimal medical therapy, defined as an antiplatelet agent, a statin, and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (if the patient had hypertension) on the patient's home medication list on admission for surgery, all of which are Class I recommendations. Despite also being Class I recommendations, cilostazol was not included in the primary exposure due to its highly selective use and our inability to capture intolerance and/or contraindications that are common, and lifestyle therapies were not included as they were only recorded at the time of discharge rather than preoperatively. The primary outcomes were mortality, hospital readmission, amputation, wound complication, myocardial infarction (MI), non-patent bypass, and non-independent ambulatory status at 30 days and 1 year after surgery. Multivariable logistic regression was performed to estimate the association of receiving optimal vs non-optimal medical therapy. A total of 3829 patients with claudication underwent bypass surgery during the study period, with a mean age of 64.8 years (standard deviation, 9.8 years); 2690 (70.3%) were males, and 1873 (48.9%) were current smokers. Of the patients, 1822 (47.6%) were on optimal medical therapy prior to surgery. Additionally, at discharge, 66.5% of smokers received referral to smoking cessation therapy, and 54.1% of patients received referral to exercise therapy. In a multivariable logistic regression, compared with patients not on optimal medical therapy, patients on optimal medical therapy prior to surgery had lower 30-day odds of mortality (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.26-0.78) and MI (aOR, 0.46; 95% CI, 0.28-0.76), lower 1-year odds of mortality (aOR, 0.57; 95% CI, 0.39-0.82), MI (aOR, 0.48; 95% CI, 0.32-0.74), and lower readmission (aOR, 0.79; 95% CI, 0.64-0.96). Although medical and lifestyle management is recommended as first-line treatment for patients with PAD, only one-half of patients were on optimal medical therapy prior to surgery. Patients receiving optimal therapy had a lower risk of postoperative mortality, MI, and readmission. This suggests that not only are there significant opportunities to improve clinical utilization of evidence-based treatment of PAD, but that doing so can benefit patients postoperatively. [ABSTRACT FROM AUTHOR]