Alterations in heart rate variability in patients with peripheral arterial disease requiring surgical revascularization have limited association with postoperative major adverse cardiovascular and cerebrovascular events.

OBJECTIVE: Obstructive sleep apnea (OSA) is common in peripheral arterial disease (PAD) and associates with high mortality after surgery. Since abnormal heart rate variability (HRV) is predictive of postoperative complications, we investigated the relations of HRV with PAD, OSA and major adverse cardiovascular and cerebrovascular events (MACCE). MATERIALS AND METHODS: Seventy-five patients (67±9 years) scheduled for sub-inguinal revascularization and 15 controls (63±6 years) underwent polysomnography and HRV analyses. OSA with an apnea-hypopnea index (AHI) ≥20/hour was considered significant. HRV was measured during wakefulness, S2, S3-4 and rapid eye movement (REM) sleep with time and frequency domain methods including beat-to-beat variability, low frequency (LF) and high frequency (HF) power, and detrended fluctuation analysis (DFA). MACCE was defined as cardiac death, myocardial infarction, coronary revascularization, hospitalized angina pectoris and stroke. RESULTS: Thirty-six patients (48%) had AHI≥20/hour. During follow-up (median 52 months), 22 patients (29%) suffered a MACCE. Compared to controls, fractal correlation of HRV (scaling exponent alpha 1 measured with DFA) was weaker during S2 and evening wakefulness in all subgroups (+/-AHI≥20/hour, +/-MACCE) but only in patients with AHI≥20/hour during morning wakefulness. The LF/HF ratio was lower in all subgroups during S2 but only in patients with AHI ≥20/hour during evening or morning wake. In the covariance analysis adjusted for age, body mass index, coronary artery disease and PAD duration, the alpha 1 during morning wakefulness remained significantly lower in patients with AHI≥20/hour than in those without (1.12 vs. 1.45; p = 0.03). Decreased HF during REM (p = 0.04) and S3-4 sleep (p = 0.03) were predictive of MACCE. In analyses with all sleep stages combined, mean heart rate as well as very low frequency, LF, HF and total power were associated with OSA of mild-to-moderate severity (AHI 10-20/hour). CONCLUSIONS: HRV is altered in patients with PAD. These alterations have a limited association with OSA and MACCE.

Osteointegration of PLGA implants with nanostructured or microsized ß-TCP particles in a minipig model.

Bioresorbable suture anchors and interference screws have certain benefits over equivalent titanium-alloy implants. However, there is a need for compositional improvement of currently used bioresorbable implants. We hypothesized that implants made of poly(l-lactide-co-glycolide) (PLGA) compounded with nanostructured particles of beta-tricalcium phosphate (ß-TCP) would induce stronger osteointegration than implants made of PLGA compounded with microsized ß-TCP particles. The experimental nanostructured self-reinforced PLGA (85L:15G)/ß-TCP composite was made by high-energy ball-milling. Self-reinforced microsized PLGA (95L:5G)/ß-TCP composite was prepared by melt-compounding. The composites were characterized by gas chromatography, Ubbelohde viscometry, scanning electron microscopy, laser diffractometry, and standard mechanical tests. Four groups of implants were prepared for the controlled laboratory study employing a minipig animal model. Implants in the first two groups were prepared from nanostructured and microsized PLGA/ß-TCP composites respectively. Microroughened titanium-alloy (Ti6Al4V) implants served as positive intra-animal control, and pure PLGA implants as negative control. Cone-shaped implants were inserted in a random order unilaterally in the anterior cortex of the femoral shaft. Eight weeks after surgery, the mechanical strength of osteointegration of the implants was measured by a push-out test. The quality of new bone surrounding the implant was assessed by microcomputed tomography and histology. Implants made of nanostructured PLGA/ß-TCP composite did not show improved mechanical osteointegration compared with the implants made of microsized PLGA/ß-TCP composite. In the intra-animal comparison, the push-out force of two PLGA/ß-TCP composites was 35-60% of that obtained with Ti6Al4V implants. The implant materials did not result in distinct differences in quality of new bone surrounding the implant.

Sleep apnoea is associated with major cardiac events in peripheral arterial disease.

Obstructive sleep apnoea (OSA) is associated with atherosclerosis and cardiovascular events. Peripheral arterial disease (PAD) represents severe atherosclerosis with a high mortality after vascular surgery. The role of OSA in the prognosis of these patients is not yet established. 84 patients (aged 67 ± 9 years) scheduled for sub-inguinal surgical revascularisation were enrolled for preoperative polysomnography. The threshold for significant OSA was an apnoea/hypopnoea index ≥ 20 events·h(-1). Major adverse cardiovascular and cerebrovascular events (MACCE), including cardiac death, myocardial infarction, coronary revascularisation, angina pectoris requiring hospitalisation and stroke, were used as a combined end-point. During follow-up (median 52 months), 17 out of 39 patients with and six out of 45 patients without significant OSA suffered MACCE. In the multivariate Cox regression, the primary predictors of MACCE were significant OSA (hazard ratio (HR) 5.1 (95% CI 1.9-13.9); p=0.001) and pre-existing coronary artery disease (HR 4.4 (95% CI 1.8-10.6); p=0.001). Other significant predictors were a ≥ 4 year history of PAD (HR 3.8 (95% CI 1.3-11.5); p=0.02) and decreasing high-density lipoprotein/total cholesterol ratio (HR 0.95 per percentage (95% CI 0.90-1.00); p=0.048). OSA is associated with poor long-term outcome in patients with PAD following revascularisation. OSA might have an important role in the pathogenesis of cardiovascular morbidity and mortality in these patients.

Unrecognised obstructive sleep apnoea is common in severe peripheral arterial disease.

Patients needing surgery for peripheral arterial disease (PAD) represent a severe form of atherosclerosis with an overall 5-yr mortality of 30% after revascularisation. The aetiology for poor post-operative clinical outcome in these high-risk patients is not fully established. Obstructive sleep apnoea (OSA) is associated with atherosclerosis and is an independent risk factor for fatal and nonfatal cardiac events. Here, we determine the prevalence of undiagnosed OSA in a homogenous group of PAD patients undergoing subinguinal surgical revascularisation. 82 consecutive patients (mean age 67±9 yrs, 52 males) with sinus rhythm and without congestive heart failure or previously diagnosed OSA were enrolled for pre-operative polysomnography and echocardiography. OSA was present in 70 (85%) patients (95% CI 75-93%), of whom 24 (34%) had severe OSA. OSA was mostly asymptomatic, and age- and sex-adjusted multivariate regression analysis showed no relation to obesity, metabolic syndrome or any manifestation of atherosclerosis, other than PAD. Left ventricular ejection fraction (p = 0.002) and high-density lipoprotein/total cholesterol ratio (p = 0.03) were the only independent predictors for the severity of OSA. Thus, prevalence of OSA is unexpectedly high in patients with PAD and is not related to classical risk factors of sleep apnoea.

The effect of body mass index on the spread of spinal block in patients with rheumatoid arthritis.

PURPOSE: Body mass index (BMI) has a significant effect on the spread of sensory spinal block in rheumatoid patients. We tried to achieve the same spread of spinal block for patients in three different BMI groups and, on the basis of the results from a preliminary study, used a simple method feasible for clinical practice. We hypothesized that BMI-related inverse dosing of plain bupivacaine according to low, normal, and high BMI would result in no difference in block extent. METHODS: Together 75 patients with seropositive rheumatoid arthritis were included in three equal-sized groups according to BMI: low (<23 kg/m(2)), normal (23-28 kg/m(2)), and high (>28 kg/m(2)). Spinal anesthesia was induced with plain bupivacaine using doses 3.3, 3.0, and 2.7 ml, respectively. The spread of sensory block was recorded 30 min after injection of bupivacaine by use of a pin-prick test and a cold ice-filled container. RESULTS: Spreads of sensory block were different in low, normal, and high BMI groups (mean (SD); 14.0 (2.6), 14.5 (2.5), and 16.3 (2.5) dermatomes, respectively, P = 0.006) because of greater block extent in the high-BMI group. CONCLUSIONS: Despite three-step dosing of plain bupivacaine inversely related to BMI (low, normal, or high), comparable block extent was not achieved because of greater spread in the high-BMI group. Adjustment of plain bupivacaine dose according to BMI could be used to achieve a more predictable spread of spinal block, but further reduction of dose is needed in patients with high BMI.

Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function.

BACKGROUND: Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties. METHODS: This prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2 microg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted. RESULTS: The groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9 (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112). CONCLUSIONS: Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased.