The Use of Intraoperative Transit Time Flow Measurement for Coronary Artery Bypass Surgery: Systematic Review of the Evidence and Expert Opinion Statements.

Transit time flow measurement (TTFM) allows quality control in coronary artery bypass grafting but remains largely underused, probably because of limited information and the lack of standardization. We performed a systematic review of the evidence on TTFM and other methods for quality control in coronary artery bypass grafting following PRISMA standards and elaborated expert recommendations by using a structured process. A panel of 19 experts took part in the consensus process using a 3-step modified Delphi method that consisted of 2 rounds of electronic voting and a final face-to-face virtual meeting. Eighty percent agreement was required for acceptance of the statements. A 2-level scale (strong, moderate) was used to grade the statements based on the perceived likelihood of a clinical benefit. The existing evidence supports an association between TTFM readings and graft patency and postoperative clinical outcomes, although there is high methodological heterogeneity among the published series. The evidence is more robust for arterial, rather than venous, grafts and for grafts to the left anterior descending artery. Although TTFM use increases the duration and the cost of surgery, there are no data to quantify this effect. Based on the systematic review, 10 expert statements for TTFM use in clinical practice were formulated. Six were approved at the first round of voting, 3 at the second round, and 1 at the virtual meeting. In conclusion, although TTFM use may increase the costs and duration of the procedure and requires a learning curve, its cost/benefit ratio seems largely favorable, in view of the potential clinical consequences of graft dysfunction. These consensus statements will help to standardize the use of TTFM in clinical practice and provide guidance in clinical decision-making.

Current status of intra-operative graft assessment: Should it be the standard of care for coronary artery bypass graft surgery?

The "Achilles heel" of coronary artery bypass graft (CABG) surgery is graft patency. While long-term patency is determined by the type of conduit and the progression of graft and native vessel disease, short-term patency is affected by intra-operative technical issues. Transit-time flow measurements and epicardial ultrasound have been shown to accurately assess intra-operative graft patency. This review will examine the evidence to support the premise that intra-operative graft assessment is essential in determining graft patency and should be the standard of care when performing CABG surgery.

Graft quality verification in coronary artery bypass graft surgery: how, when and why?

PURPOSE OF REVIEW: The coronary artery bypass graft (CABG) operation is one of the few remaining operations/interventions on diseased arteries that are not routinely verified during or immediately after the procedure. This review answers the 'how', 'when' and 'why' of intraoperative CABG assessment. RECENT FINDINGS: More recent than new literature on this topic, is the increased interest in quality assurance of CABG. This is most likely due to reports in the last 5 years suggesting CABG superiority to percutaneous coronary intervention (PCI) for improved mid-term and long-term outcomes; for example, for patients with diabetes mellitus (Freedom Trial by Farkouh in 2012), and for patients with SYNTAX score ≥ 33 (SYNTAX Trial by Mohr in 2013). Possibly CABG is re-emerging from the era-of-better-and-better-stents and is now deemed worthy of improvement. SUMMARY: In order to fully compliment PCI, the operative major adverse cardiac event rate of CABG must rival that of PCI. In order to reduce technical errors, it is best practice to perform intra-operative assessment of bypasses, especially since we have the tools.

A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery.

BACKGROUND: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. METHODS: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer-Lemeshow goodness-of-fit test and Net Reclassification Improvement index. RESULTS: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00-4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15-2.40), diabetes mellitus (1.61, 1.12-2.31), baseline estimated glomerular filtration rate (0.96, 0.95-0.97), increasing hemoglobin concentration (0.85, 0.77-0.93), proteinuria (1.65, 1.07-2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64-2.43), other cardiac procedure (v. CABG only, 3.11, 2.12-4.58) and emergent status for surgery booking (4.63, 2.61-8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79-0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). INTERPRETATION: We have developed and validated a practical and accurate risk prediction model for acute kidney injury requiring renal replacement therapy after cardiac surgery based on routinely available preoperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.

BACKGROUND: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. METHODS: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. RESULTS: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). INTERPRETATION: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01071265.

Coronary artery bypass grafting: Part 1--the evolution over the first 50 years.

Surgical treatment for angina pectoris was first proposed in 1899. Decades of experimental surgery for coronary artery disease finally led to the introduction of coronary artery bypass grafting (CABG) in 1964. Now that we are approaching 50 years of CABG experience, it is appropriate to summarize the advancement of CABG into a procedure that is safe and efficient. This review provides a historical recapitulation of experimental surgery, the evolution of the surgical techniques and the utilization of CABG. Furthermore, data on contemporary clinical outcomes are discussed.

Coronary artery bypass grafting: Part 2--optimizing outcomes and future prospects.

Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG) has become the standard of care for patients with coronary artery disease. Surprisingly, the fundamental surgical technique itself did not change much over time. Nevertheless, outcomes after CABG have dramatically improved over the first 50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to CABG have shown converging outcomes for select patient populations, providing more evidence for wider use of PCI. It is increasingly important to focus on the optimization of the short- and long-term outcomes of CABG and to reduce the level of invasiveness of this procedure. This review provides an overview on how new techniques and widespread consideration of evolving strategies have the potential to optimize outcomes after CABG. Such developments include off-pump CABG, clampless/anaortic CABG, minimally invasive CABG with or without extending to hybrid procedures, arterial revascularization, endoscopic vein harvesting, intraprocedural epiaortic scanning, graft flow assessment, and improved secondary prevention measures. In addition, this review represents a framework for future studies by summarizing the areas that need more rigorous clinical (randomized) evaluation.

Arterial grafting and complete revascularization: challenge or compromise?

PURPOSE OF REVIEW: Arterial grafting is superior to venous grafting in coronary artery bypass graft surgery with respect to graft patency and long-term patient outcome, but it may be difficult to achieve complete arterial revascularization. RECENT FINDINGS: Use of arterial grafts, especially bilateral internal mammary artery grafts, is not common, whereas there are clear indications that it may increase survival. Definitions of complete revascularization are varied and confusing, making study comparisons difficult. Technical challenges in complete revascularization with arterial grafts can be minimized by surgical techniques. Competitive flow in moderately stenosed coronary arteries grafted with arterial conduits may result in reduced patency. While internal mammary arteries may be used in arteries with at least 60% stenosis, radial artery and gastroepiploic grafts are best placed onto coronaries with severe stenosis. Moderate lesions in the left coronary circulation should be bypassed, but right coronary artery lesions can be left untouched as there is minimal progression over time. Complete revascularization may not be necessary or possible in every patient because of technical challenges. CONCLUSION: Complete revascularization with arterial grafts presents both technical and physiological challenges. However, with techniques to maximize length of arterial conduits, knowledge of competitive flow and which moderate lesions should be addressed, complete revascularization with arterial grafts can be accomplished in the majority of patients, notwithstanding it may not be possible or even indicated for every patient.

Cardiac surgery elicits pericardial inflammatory responses that are distinct compared with postcardiopulmonary bypass systemic inflammation.

Objectives: Cardiac surgery using cardiopulmonary bypass contributes to a robust systemic inflammatory process. Local intrapericardial postsurgical inflammation is believed to trigger important clinical implications, such as postoperative atrial fibrillation and postsurgical intrathoracic adhesions. Immune mediators in the pericardial space may underlie such complications. Methods: In this prospective pilot clinical study, 12 patients undergoing isolated coronary artery bypass graft surgery were enrolled. Native pericardial fluid and venous blood samples (baseline) were collected immediately after pericardiotomy. Postoperative pericardial fluid and venous blood samples were collected 48-hours after cardiopulmonary bypass and compared with baseline. Flow cytometry determined proportions of specific immune cells, whereas multiplex analysis probed for inflammatory mediators. Results: Neutrophils are the predominant cells in both the pericardial space and peripheral blood postoperatively. There are significantly more CD163lo macrophages in blood compared with pericardial effluent after surgery. Although there are significantly more CD163hi macrophages in native pericardial fluid compared with baseline blood, after surgery there are significantly fewer of these cells present in the pericardial space compared with blood. Postoperatively, concentration of interleukin receptor antagonist 6, and interleukin 8 were significantly higher in the pericardial space compared with blood. After surgery, compared with blood, the pericardial space has a significantly higher concentration of matrix metalloproteinase 3, matrix metalloproteinase 8, and matrix metalloproteinase 9. The same trend was observed with transformational growth factor ß. Conclusions: Cardiac surgery elicits an inflammatory response in the pericardial space, which differs from systemic inflammatory responses. Future work should determine whether or not this distinct local inflammatory response contributes to postsurgical complications and could be modified to influence clinical outcomes.

Expiratory and inspiratory action of transversus abdominis during eupnea and hypercapnic ventilation.

BACKGROUND: Recently, there is interest in the clinical importance of monitoring abdominal muscles during respiratory failure. The clinical interpretation relies on the assumption that expiration is a passive physiologic process and, since diaphragm and abdomen are arranged in series, any inward motion of the abdominal wall represents a sign of diaphragm dysfunction. However, previous studies suggest transversus abdominis might be active even during eupnea and is preferentially recruited over the other abdominal muscles. OBJECTIVE: 1) Is transversus abdominis normally recruited during eupnea? 2) What is the degree of activation of transversus abdominis during hypercapnia? 3) Does the end-inspiratory length of transversus abdominis change during hypercapnia, while diaphragm function is normal? METHODS: In 30 spontaneously breathing canines, awake without confounding anesthetic, we measured directly both electrical activity and corresponding mechanical length and shortening of transversus abdominis during eupnea and hypercapnia. RESULTS: Transversus abdominis is consistently recruited during eupnea. During hypercapnia, transversus abdominis recruitment is progressive and significant. Throughout hypercapnia, transversus abdominis baseline end-inspiratory length is not constant: baseline length decreases progressively throughout hypercapnia. After expiration, into early inspiration, transversus abdominis shows a consistent neural mechanical post -expiratory expiratory activity (PEEA) at rest, which progressively increases during hypercapnia. CONCLUSION: Transversus abdominis is an obligatory expiratory muscle, reinforcing the fundamental principle expiration is not a passive process. Beyond expiration, during hypercapnic ventilation, transversus abdominis contributes as an "accessory inspiratory muscle" into the early phase of inspiration. Clinical monitoring of abdominal wall motion during respiratory failure may be confounded by action of transversus abdominis.

Graft flow evaluation with intraoperative transit-time flow measurement in off-pump versus on-pump coronary artery bypass grafting.

Objective: We aimed to compare transit-time flow measurement (TTFM) parameters for on-pump (ONCAB) and off-pump (OPCAB) coronary artery bypass procedures. Methods: The database of the Registry for Quality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery (REQUEST) study was retrospectively reviewed. Only single grafts were included (ie, no sequential or Y/T grafts). Primary end points were mean graft flow (MGF), pulsatility index (PI), diastolic fraction (DF), and backflow (BF). Unadjusted and propensity score-matching comparisons were performed. Results: Of 1016 patients in the REQUEST registry, 846 had at least 1 graft for which TTFM was performed. Of these, 512 patients (60.6%) underwent ONCAB and 334 (39.4%) OPCAB procedures. Mean arterial pressure (MAP) during measurements was higher in the OPCAB group. After propensity score-matching, 312 well balanced pairs were left. In these matched patients, MGF was higher for the ONCAB versus the OPCAB group (32 vs 28 mL/min, respectively, for all grafts [P < .001]; 30 vs 27 mL/min for arterial grafts [P = .002]; and 35 vs 31 mL/min for venous grafts [P = .006], respectively). PI was lower in the ONCAB group (2.1 vs 2.3, for all grafts; P < .001). Diastolic fraction was slightly lower in the ONCAB group (65% vs 67.5%; P < .001). The backflow was also lower in the ONCAB group (0.6 vs 1.3; P < .001) with trends similar to MGF and PI for venous and arterial grafts. There were 21 (3.3%) revisions in the OPCAB group and 14 (2.1%) in the ONCAB group (P = .198). Conclusions: ONCAB surgery was associated with higher MGF and lower PI values, especially in venous grafts. Different TTFM cutoff values for ONCAB versus OPCAB surgery might be considered.

Comprehensive characterization of the postoperative pericardial inflammatory response: Potential implications for clinical outcomes.

Objective: There is a paucity of data on the inflammatory response that takes place in the pericardial space after cardiac surgery. This study provides a comprehensive assessment of the local postoperative inflammatory response. Methods: Forty-three patients underwent cardiotomy, where native pericardial fluid was aspirated and compared with postoperative pericardial effluent collected at 4, 24, and 48 hours' postcardiopulmonary bypass. Flow cytometry was used to define the levels and proportions of specific immune cells. Samples were also probed for concentrations of inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). Results: Preoperatively, the pericardial space mainly contains macrophages and T cells. However, the postsurgical pericardial space was populated predominately by neutrophils, which constituted almost 80% of immune cells present, and peaked at 24 hours. When surgical approaches were compared, minimally invasive surgery was associated with fewer neutrophils in the pericardial space at 4 hours' postsurgery. Analysis of the intrapericardial concentrations of inflammatory mediators showed interleukin-6, MMP-9, and TIMP-1 to be highest postsurgery. Over time, MMP-9 concentrations decreased significantly, whereas TIMP-1 levels increased, resulting in a significant reduction of the ratio of MMP:TIMP after surgery, suggesting that active inflammatory processes may influence extracellular matrix remodeling. Conclusions: These results show that cardiac surgery elicits profound alterations in the immune cell profile in the pericardial space. Defining the cellular and molecular mediators that drive pericardial-specific postoperative inflammatory processes may allow for targeted therapies to reduce immune-mediated complications.

Costs and consequences of acute kidney injury after cardiac surgery: A cohort study.

OBJECTIVES: Acute kidney injury (AKI) is common after cardiac surgery. We quantified the mortality and costs of varying degrees of AKI using a population-based cohort in Alberta, Canada. METHODS: A cohort of patients undergoing cardiac surgery from 2004 to 2009 was assembled from linked Alberta administrative databases. AKI was classified by Kidney Disease Improving Global Outcomes stages of severity. Our outcomes were in-hospital mortality, length of stay, and costs; among survivors, we also examined mortality and costs at 365 days. Estimates were adjusted for demographic characteristics, comorbidities, and other covariates. RESULTS: Ten thousand one hundred seventy participants were included, of whom 9771 patients were discharged to community. Overall in-hospital mortality, costs, and length of stay were 4%, 7 days, and Can $34,000, respectively. Postcardiac surgery, AKI occurred in 25%. Compared with those without AKI, AKI was independently associated with increased in-hospital mortality across severity categories, with the highest risk (adjusted odds ratio, 37.1; 95% confidence interval, 26.3-52.1; P < .001) in patients who required acute dialysis. AKI severity was associated with increased hospital days and costs, with costs ranging from 1.21 for stage 1 AKI (95% confidence interval, 1.17-1.23) to 2.74 for acute dialysis (95% confidence interval, 2.49-3.00) (P < .001) times higher than in patients without AKI, after covariate adjustment. Postdischarge to 365 days, patients with AKI continued to experience increased costs up to 1.35-fold, and patients who required dialysis acutely continued to experience a 2.86-fold increased mortality. CONCLUSIONS: AKI remains an important indicator of mortality and health care costs postcardiac surgery.

Intraoperative transit-time flow measurement and high-frequency ultrasound in coronary artery bypass grafting: impact in off versus on-pump, arterial versus venous grafting and cardiac territory grafted.

OBJECTIVES: Despite society guideline recommendations, intraoperative high-frequency ultrasound (HFUS) and transit-time flow measurement (TTFM) use in coronary artery bypass grafting (CABG) has not been widely adopted worldwide. This retrospective review of the REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study assesses the impact of protocolled high-frequency ultrasound/TTFM use in specific technical circumstances of CABG. METHODS: Three REQUEST study sub-analyses were examined: (i) For off-pump (OPCAB) versus on-pump (ONCAB) procedures: strategy changes from preoperative plans for the aorta, conduits, coronary targets and graft revisions; and for all REQUEST patients, revision rates in: (ii) arterial versus venous grafts; and (iii) grafts to different cardiac territories. RESULTS: Four hundred and two (39.6%) of 1016 patients undergoing elective isolated CABG for multivessel disease underwent OPCAB procedures. Compared to ONCAB, OPCAB patients experienced more strategy changes regarding the aorta [14.7% vs 3.4%; odds ratios (OR) = 4.03; confidence interval (CI) = 2.32-7.20], less regarding conduits (0.2% vs 2.8%; OR = 0.09; CI = 0.01-0.56), with no differences in coronary target changes or graft revisions (4.1% vs 3.5%; OR = 1.19; CI = 0.78-1.81). In all REQUEST patients, revisions were more common for arterial versus venous grafts (4.7% vs 2.4%; OR = 2.05; CI = 1.29-3.37), and inferior versus anterior (5.1% vs 2.9%; OR = 1.77; CI = 1.08-2.89) and lateral (5.1% vs 2.8%; OR = 1.83; CI = 1.04-3.27) territory grafts. CONCLUSIONS: High-frequency ultrasound/TTFM use differentially impacts strategy changes and graft revision rates in different technical circumstances of CABG. Notably, patients undergoing OPCAB experienced 4 times more changes related to the ascending aorta than ONCAB patients. These findings may indicate where intraoperative assessment is most usefully applied. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02385344.

Intraoperative surgical strategy changes in patients with chronic and end-stage renal disease undergoing coronary artery bypass grafting.

OBJECTIVES: Factors such as more diffuse atherosclerosis, plaque instability and accelerated vascular calcification in patients with chronic and end-stage renal disease (ESRD) can potentially present intraoperative challenges in coronary artery bypass grafting (CABG) procedures. We evaluated whether patients with chronic and ESRD experienced more surgical strategy changes and/or graft revisions than patients with normal renal function when undergoing CABG procedures according to a protocol for intraoperative high-frequency ultrasound and transit-time flow measurement (TTFM). METHODS: Outcomes of CABG for patients with chronic and ESRD and patients with normal renal function enrolled in the multicentre prospective REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study were compared retrospectively. The primary end point was frequency of intraoperative surgical strategy changes. The secondary end point was post-protamine TTFM parameters. RESULTS: There were 95 patients with chronic and ESRD and 921 patients with normal renal function. Patients with chronic and ESRD undergoing CABG according to a protocol for intraoperative high-frequency ultrasound and TTFM had a higher rate of strategy changes overall [33.7% vs 24.3%; odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.01-2.48; P = 0.047] and greater revisions per graft (7.0% vs 3.4%; odds ratio = 2.14; 95% CI = 1.17-3.71; P = 0.008) compared to patients with normal renal function. Final post-protamine graft TTFM parameters were comparable between cohorts. CONCLUSIONS: Patients with chronic and ESRD undergoing CABG procedures with high-frequency ultrasound and TTFM experience more surgical strategy changes than patients with normal renal function while achieving comparable graft flow. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02385344.

KCa channel activation normalizes endothelial function in Type 2 Diabetic resistance arteries by improving intracellular Ca2+ mobilization.

BACKGROUND: Endothelial dysfunction is an early pathogenic event in the progression of cardiovascular disease in patients with Type 2 Diabetes (T2D). Endothelial KCa2.3 and KCa3.1 K+ channels are important regulators of arterial diameter, and we thus hypothesized that SKA-31, a small molecule activator of KCa2.3 and KCa3.1, would positively influence agonist-evoked dilation in myogenically active resistance arteries in T2D. METHODOLOGY: Arterial pressure myography was utilized to investigate endothelium-dependent vasodilation in isolated cremaster skeletal muscle resistance arteries from 22 to 24 week old T2D Goto-Kakizaki rats, age-matched Wistar controls, and small human intra-thoracic resistance arteries from T2D subjects. Agonist stimulated changes in cytosolic free Ca2+ in acutely isolated, single endothelial cells from Wistar and T2D Goto-Kakizaki cremaster and cerebral arteries were examined using Fura-2 fluorescence imaging. MAIN FINDINGS: Endothelium-dependent vasodilation in response to acetylcholine (ACh) or bradykinin (BK) was significantly impaired in isolated cremaster arteries from T2D Goto-Kakizaki rats compared with Wistar controls, and similar results were observed in human intra-thoracic arteries. In contrast, inhibition of myogenic tone by sodium nitroprusside, a direct smooth muscle relaxant, was unaltered in both rat and human T2D arteries. Treatment with a threshold concentration of SKA-31 (0.3 µM) significantly enhanced vasodilatory responses to ACh and BK in arteries from T2D Goto-Kakizaki rats and human subjects, whereas only modest effects were observed in non-diabetic arteries of both species. Mechanistically, SKA-31 enhancement of evoked dilation was independent of vascular NO synthase and COX activities. Remarkably, SKA-31 treatment improved agonist-stimulated Ca2+ elevation in acutely isolated endothelial cells from T2D Goto-Kakizaki cremaster and cerebral arteries, but not from Wistar control vessels. In contrast, SKA-31 treatment did not affect intracellular Ca2+ release by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor cyclopiazonic acid. CONCLUSIONS: Collectively, our data demonstrate that KCa channel modulation can acutely restore endothelium-dependent vasodilatory responses in T2D resistance arteries from rats and humans, which appears to involve improved endothelial Ca2+ mobilization.

Transit time flow measurement of coronary bypass grafts before and after protamine administration.

BACKGROUND: Intraoperative graft assessment with tools like Transit Time Flow Measurement (TTFM) is imperative for quality control in coronary surgery. We investigated the variation of TTFM parameters before and after protamine administration to identify new benchmark parameters for graft quality assessment. METHODS: The database of the REQUEST ("REgistry for QUality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery") study was retrospectively reviewed. A per graft analysis was performed. Only single grafts (i.e., no sequential nor composite grafts) where both pre- and post-protamine TTFM values were recorded with an acoustical coupling index > 30% were included. Grafts with incomplete data and mixed grafts (arterio-venous) were excluded. A second analysis was performed including single grafts only in the same MAP range pre- and post- protamine administration. RESULTS: After adjusting for MAP, we found a small increase in MGF (29 mL/min to 30 mL/min, p = 0.009) and decrease in PI (2.3 to 2.2, p <  0.001) were observed after the administration of protamine. These changes were especially notable for venous conduits and for CABG procedures performed on-pump. CONCLUSION: The small changes in TTFM parameters observed before and after protamine administration seem to be clinically irrelevant, despite being statistically significant in aggregate. Our data do not support a need to perform TTFM measurements both before and after protamine administration. A single TTFM measurement taken either before or after protamine may suffice to achieve reliable data on each graft's performance. Depending on the specific clinical situation and intraoperative changes, more measurements may be informative. TRIAL REGISTRATION: Clinical Trials Number: NCT02385344 , registered February 17th, 2015.

Intraoperative transit-time flow measurement and high-frequency ultrasound assessment in coronary artery bypass grafting.

OBJECTIVES: We evaluated the influence of transit-time flow measurement with epicardial and epiaortic high-frequency ultrasound in patients undergoing coronary artery bypass grafting procedure. METHODS: The Registry for Quality Assessment with Ultrasound Imaging and Transit-time Flow Measurement in Cardiac Bypass Surgery study is a multicenter, prospective study among 7 international centers performing coronary artery bypass grafting procedures. The primary end point was any change in the planned surgical procedure. Major secondary end points consisted of the rate and reason for surgical changes related to the aorta, in situ conduits, coronary targets, and completed grafts, and the rate of in-hospital mortality and major morbidity. RESULTS: Between April 2015 and December 2017, 1046 patients were enrolled. Of those, 1016 were included in the final analyses. Mean age was 65.9 years, 14.0% were women, and diabetes was present in 39.6%. Off-pump procedures were performed in 39.6% and bilateral internal thoracic arteries in 30.5%. The primary end point occurred in 25.2% of patients (n = 256) and in 77% (197 out of 256) this was based on transit-time flow measurement and/or high-frequency ultrasound. Surgical changes were related to the aorta in 9.9%, to in situ conduits in 2.7%, and the coronary targets in 22.6%. Graft revision occurred in 7.8%, including revisions of the proximal and/or distal anastomosis in 6.6%. In-hospital adverse event rates were 0.6% for mortality, 1.0% for cerebrovascular events, and 0.3% for myocardial infarction. CONCLUSIONS: Surgical changes related to the aorta, conduits, coronary targets, and anastomosis were made in 25% of patients. This was associated with low operative mortality and low major morbidity. Transit-time flow measurement and high-frequency ultrasound may improve the quality, safety, and efficacy of coronary artery bypass grafting procedures and should be considered as a routine procedural aspect.

Costal and crural diaphragm function during sustained hypoxia in awake canines.

In humans and other mammals, isocapnic hypoxia sustained for 20-60 min exhibits a biphasic ventilation pattern: initial increase followed by a significant ventilatory decline ("roll-off") to a lesser intermediate plateau. During sustained hypoxia, the mechanical action and activity of the diaphragm have not been studied; thus we assessed diaphragm function in response to hypoxic breathing. Thirteen spontaneously breathing awake canines were exposed to moderate levels of sustained isocapnic hypoxia lasting 20-25 min (80 ± 2% pulse oximeter oxygen saturation). Breathing pattern and changes in muscle length and electromyogram (EMG) activity of the costal and crural diaphragm were continuously recorded. Mean tidal shortening and EMG activity of the costal and crural diaphragm exhibited an overall biphasic pattern, with initial brisk increase followed by a significant decline (P < 0.01). Although costal and crural shortening did not differ significantly with sustained hypoxia, this equivalence in segmental shortening occurred despite distinct and differing EMG activities of the costal and crural segments. Specifically, initial hypoxia elicited a greater costal EMG activity compared with crural (P < 0.05), whereas sustained hypoxia resulted in a lesser crural EMG decline/attenuation than costal (P < 0.05). We conclude that sustained isocapnic hypoxia elicits a biphasic response in both ventilation and diaphragmatic function and there is clear differential activation and contribution of the two diaphragmatic segments. This different diaphragm segmental action is consistent with greater neural activation of costal diaphragm during initial hypoxia, then preferential sparing of crural activation as hypoxia is sustained. NEW & NOTEWORTHY In humans and other mammals, during isocapnic hypoxia sustained for 20-60 min ventilation exhibits a biphasic pattern: initial increase followed by significant ventilatory decline ("roll-off"). During sustained hypoxia, the function of the diaphragm is unknown. This study demonstrates that the diaphragm reveals a biphasic action during the time-dependent hypoxic "roll-off" in ventilation. These results also highlight that the two diaphragm segments, costal and crural, show differing, distinctive contributions to diaphragm function during sustained hypoxia.

Improving coronary artery bypass grafting: a systematic review and meta-analysis on the impact of adopting transit-time flow measurement.

Despite there being numerous studies of intraoperative graft flow assessment by transit-time flow measurement (TTFM) on outcomes after coronary artery bypass grafting (CABG), the adoption of contemporary TTFM is low. Therefore, on 31 January 2018, a systematic literature search was performed to identify articles that reported (i) the amount of grafts classified as abnormal or which were revised or (ii) an association between TTFM and outcomes during follow-up. Random-effects models were used to create pooled estimates with 95% confidence intervals (CI) of (i) the rate of graft revision per patient, (ii) the rate of graft revision per graft and (iii) the rate of graft revision among grafts deemed abnormal based on TTFM parameters. The search yielded 242 articles, and 66 original articles were included in the systematic review. Of those articles, 35 studies reported on abnormal grafts or graft revisions (8943 patients, 15 673 grafts) and were included in the meta-analysis. In 4.3% of patients (95% CI 3.3-5.7%, I2 = 73.9) a revision was required and 2.0% of grafts (95% CI 1.5-2.5%; I2 = 66.0) were revised. The pooled rate of graft revisions among abnormal grafts was 25.1% (95% CI 15.5-37.9%; I2 = 80.2). Studies reported sensitivity ranging from 0.250 to 0.457 and the specificity from 0.939 to 0.984. Reported negative predictive values ranged from 0.719 to 0.980 and reported positive predictive values ranged from 0.100 to 0.840. This systematic review and meta-analysis showed that TTFM could improve CABG procedures. However, due to heterogeneous data, drawing uniform conclusions appeared challenging. Future studies should focus on determining the optimal use of TTFM and assessing its diagnostic accuracy.