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Papers by David Latter

C oronary revascularisation plays an important role in the management of patients with ischaemic ... more C oronary revascularisation plays an important role in the management of patients with ischaemic heart disease. Its principle builds on restoring antegrade flow thereby relieving angina. As a result, the need for medication is reduced which, in turn, may improve quality of life and socioeconomic independency. Also the prognosis is beneficially affected. This is not only true for patients with severe coronary atherosclerosis such as patients with left main or three vessel disease, but also for patients with less advanced disease. w1-3 c WHY OFF-PUMP BYPASS SURGERY?

The Journal of thoracic and cardiovascular surgery, 2014

To demonstrate a novel, reproducible, and effective method of direct innominate artery cannulatio... more To demonstrate a novel, reproducible, and effective method of direct innominate artery cannulation using a 14 F pediatric venous cannula to establish antegrade cerebral protection (ACP) in patients undergoing aortic surgery that requires an open distal anastomosis or hemiarch replacement. We reviewed prospectively gathered data on all patients who had undergone replacement of the ascending aorta or hemiarch with an open distal anastomosis using deep hypothermic circulatory arrest and direct innominate artery cannulation with a 14 F pediatric venous cannula at our institution. After central cannulation and cooling to 25 °C to 28 °C, all patients had ACP initiated by way of a direct innominate cannula placed over a guidewire. Fifty patients underwent direct innominate artery cannulation with our technique from 2010 to 2012. The operative mortality was 2% (n = 1), and the rates of neurologic morbidity were acceptable and similar to those with other methods of ACP delivery: stroke (2%, ...

The Canadian journal of cardiology, 2014

This position statement addresses issues in revascularization for multivessel coronary artery dis... more This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life. One purpose of this document is to propose practical multidisciplinary approaches to the management of these patients. Recommendations are made for revascularization in ac...

The Journal of Thoracic and Cardiovascular Surgery, 2011

Recombinant factor VIIa can decrease postoperative bleeding after cardiac surgery. However, the p... more Recombinant factor VIIa can decrease postoperative bleeding after cardiac surgery. However, the potential for recombinant factor VIIa to cause early vascular graft occlusion at the site of new vascular anastomoses has not been fully explored. We hypothesized that recombinant factor VIIa would cause a dose-dependent reduction in vascular graft patency in rabbits. Reversed end-to-end interpositional vein grafts were sutured into the carotid artery of heparinized rabbits, and then recombinant factor VIIa (300 μg/kg, 90 μg/kg, or 20 μg/kg intravenously) or placebo was administered (n = 16/group). Graft patency was assessed at 24 hours using a vascular ultrasound probe. Factor VII activity levels were measured using a prothrombin time-based assay. In different rabbits, the patency of venous end-to-side anastomoses and simple carotid arterial repairs was assessed (recombinant factor VIIa, 300 μg/kg vs placebo, n = 8/group). Data were analyzed using Fisher's exact test, t tests, or analysis of variance. Physiologic variables (activated clotting time, hemoglobin, pH, Pao(2)) and vessel diameter were not different between groups. Vein graft patency was reduced (93.8%, 81.2%, 13.8%, and 6.3%) as factor VII activity levels increased (1.8 ± 0.4, 4.4 ± 2.1, 11.8 ± 4.7, and 23.6 ± 16.9 U/mL, respectively) with increasing doses of recombinant factor VIIa administered (0, 20, 90, and 300 μg/kg, respectively, P < .05). Patency in the arterial repairs and end-to-side venous grafts was also reduced in recombinant factor VIIa-treated rabbits (P < .05 for both). This study suggests that recombinant factor VIIa is associated with a dose-dependent increase in fresh vascular graft occlusion. Higher doses of recombinant factor VIIa may be associated with increased thrombotic outcomes.

The Journal of Thoracic and Cardiovascular Surgery, 2011

Many surgeons consider the tricuspid valve to be a second-class structure. Our objective was to d... more Many surgeons consider the tricuspid valve to be a second-class structure. Our objective was to determine the normal anatomy and dynamic characteristics of the tricuspid valve apparatus in vivo and to discern whether this would aid the design of a tricuspid valve annuloplasty ring model. Sixteen sonomicrometry crystals were placed around the tricuspid annulus, at the bases and tips of the papillary muscles, the free edges of the leaflets, and the right ventricular apex during cardiopulmonary bypass in 5 anesthetized York Hampshire pigs. Animals were studied after weaning of cardiopulmonary bypass on 10 cardiac cycles of normal hemodynamics. Sonomicrometry array localizations demonstrate the multiplanar shape of the tricuspid annulus. The tricuspid annulus reaches its maximum area (97.9 ± 25.4 mm(2)) at the end of diastole and its minimum area (77.3 ± 22.5 mm(2)) at the end of systole, and increases again in early diastole. Papillary muscles shorten by 0.8 to 1.5 mm (11.2%) in systole, and chordae tendineae straighten by 0.8 to 1.7 mm (11.4%) in systole. The shape of the tricuspid annulus is a multiplanar 3-dimensional one with its highest point at the anteroseptal commissure and its lowest point at the posteroseptal commissure, and the anteroposterior commissure is in a middle plane in between. The tricuspid annulus area reaches its maximum during diastole and its minimum during systole. The papillary muscles contract by the same amount of chordal straightening. The optimal tricuspid annuloplasty ring may be a multiplanar 3-dimensional one that mimics the normal tricuspid annulus.

Journal of Cardiothoracic Surgery, 2011

Background: Median sternotomy infection and bony nonunion are two commonly described complication... more Background: Median sternotomy infection and bony nonunion are two commonly described complications which occur in 0.4 -5.1% of cardiac procedures. Although relatively infrequent, these complications can lead to significant morbidity and mortality. The aim of this retrospective study is to evaluate the initial experience of a transverse plate fixation system following wound complications associated with sternal dehiscence with or without infection following cardiac surgery. Methods: A retrospective chart review of 40 consecutive patients who required sternal wound reconstruction post sternotomy was performed. Soft tissue debridement with removal of all compromised tissue was performed. Sternal debridement was carried using ronguers to healthy bleeding bone. All patients underwent sternal fixation using three rib plates combined with a single manubrial plate (Titanium Sternal Fixation System ® , Synthes). Incisions were closed in a layered fashion with the pectoral muscles being advanced to the midline. Data were expressed as mean ± SD, Median (range) or number (%). Statistical analyses were made by using Excel 2003 for Windows (Microsoft, Redmond, WA, USA). Results: There were 40 consecutive patients, 31 males and 9 females. Twenty two patients (55%) were diagnosed with sternal dehiscence alone and 18 patients (45%) with associated wound discharge. Thirty eight patients went on to heal their wounds. Two patients developed recurrent wound infection and required VAC therapy. Both were immunocompromised. Median post-op ICU stay was one day with the median hospital stay of 18 days after plating. Conclusion: Sternal plating appears to be an effective option for the treatment of sternal wound dehiscence associated with sternal instability. Long-term follow-up and further larger studies are needed to address the indications, benefits and complications of sternal plating.

Journal of Cardiothoracic Surgery, 2009

Background: Diffuse microvascular bleeding remains a common problem after cardiac procedures.

JACC: Cardiovascular Interventions, 2008

Objectives The purpose of this study was to compare outcomes for drug-eluting stents (DES) and co... more Objectives The purpose of this study was to compare outcomes for drug-eluting stents (DES) and coronary artery bypass graft (CABG) surgery in patients with unprotected left main coronary artery (ULMCA) stenosis.

Echocardiography, 1985

Albumin is commonly used as a volume expander in cardiopulmonary bypass (CPB) prime. Pentastarch,... more Albumin is commonly used as a volume expander in cardiopulmonary bypass (CPB) prime. Pentastarch, a low molecular weight hetastarch, may provide similar efficacy at decreased cost but is known to alter coagulation profiles. Infectious concerns forced the temporary withdrawal of albumin in our institution. Therefore we evaluated pentastarch as an alternative with regards to perioperative hemostasis and blood loss. One hundred consecutive adult patients undergoing first-time aorto-coronary bypass were given 750 mL of 10% pentastarch (represented as P in calculations) diluted in 1000 mL of Ringer's solution added in their CPB prime. A similar control group of 100 consecutive patients had received 200 mL of 25% albumin (represented as A in calculations) diluted in 1500 mL of Ringer's solution. Postoperative prothrombin time (PT) was slightly higher with pentastarch (P: 14.9 +/- 1.5 seconds, A: 14.2 +/- 1.3 seconds, p = 0.003). Postoperative bleeding was also increased (P: 2337 +/- 1242 mL, A: 1981 +/- 1121 mL, p = 0.034), mostly because of recirculated shed mediastinal blood (P: 834 +/- 499 mL, A: 640 +/- 388, p = 0.002) rather than lost pleural tube blood (P: 1503 +/- 821 mL, A: 1341 +/- 824 mL, p = 0.16). Overall net blood loss (P: 2014 +/- 914 mL, A: 2061 +/- 1015, p = 0.73) was similar. Blood-product transfusion requirements and postoperative daily hematocrits did not differ. The diminished coagulability associated with this dose of pentastarch resulted in increased postoperative bleeding. However, with recirculation of shed mediastinal blood, there was no net increase in blood loss. In this setting, pentastarch may serve as a suitable alternative to albumin.

Canadian Journal of Cardiology, 2010

Myocardial ischemia triggers the expression of multiple angiogenic factors including vascular end... more Myocardial ischemia triggers the expression of multiple angiogenic factors including vascular endothelial growth factor and its receptors. However, vascular endothelial growth factor does not act in isolation. To identify other genes important in the angiogenic response to clinically relevant myocardial ischemia. Paired intraoperative biopsies of ischemic and nonischemic myocardium were obtained from 12 patients with acute coronary syndromes (ACS) undergoing urgent coronary artery bypass graft surgery. Real-time polymerase chain reaction demonstrated significant upregulation of angiopoietin-2 (Ang-2) in ischemic myocardium, to a greater extent than other classical angiogenic factors. Microarray gene profiling identified Ang-2 to be among the top 10 differentially upregulated genes, in addition to genes involved in inflammation, cell signalling, remodelling and apoptosis. The present document is the first report of microarray analysis of patients with ACS, and supports an important role for Ang-2 in the angiogenic response to severe ischemia in the human heart. Common gene expression patterns in ACS may provide opportunities for targeted pharmacological and cellular intervention.

The Annals of Thoracic Surgery, 1996

Infusion of shed mediastinal blood using an autotransfusion system is a widely applied technique ... more Infusion of shed mediastinal blood using an autotransfusion system is a widely applied technique of blood conservation in cardiac surgery. Serial determinations of serum creatine kinase (CK), its MB isoenzyme (CK-MB), and lactate hydrogenase (LDH) levels have been used to monitor perioperative myocardial injury. We investigated the impact of postoperative autotransfused blood infusion on serum levels of these enzymes. We performed a retrospective analysis of postoperative serum CK, CK-MB, and LDH levels of 300 patients who had elective uncomplicated aortocoronary bypass grafting. Shed mediastinal blood samples from 26 patients were analyzed for CK, CK-MB (enzymatic activity and mass), and LDH levels before infusion. High postoperative serum levels of CK and LDH were observed after infusion of autotransfused blood. Shed mediastinal blood contained extremely high levels of these enzymes, particularly from patients who had internal mammary artery dissection. There was a strong correlation (r = 0.96) between measured CK-MB enzyme activities and those calculated from the CK-MB mass units. Infusion of autotransfused blood containing high concentrations of CK and LDH results in elevated serum levels of these enzymes. Hemolysis, frequently present in shed blood, does not interfere with the routine biochemical assays for CK and CK-MB enzyme activities. Caution should be taken when postoperative cardiac enzyme levels are used to determine myocardial injury after aortocoronary bypass grafting if autotransfusion is used as a method of blood conservation.

PLOS ONE, 2015

We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembr... more We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

C oronary revascularisation plays an important role in the management of patients with ischaemic ... more C oronary revascularisation plays an important role in the management of patients with ischaemic heart disease. Its principle builds on restoring antegrade flow thereby relieving angina. As a result, the need for medication is reduced which, in turn, may improve quality of life and socioeconomic independency. Also the prognosis is beneficially affected. This is not only true for patients with severe coronary atherosclerosis such as patients with left main or three vessel disease, but also for patients with less advanced disease. w1-3 c WHY OFF-PUMP BYPASS SURGERY?

The Journal of thoracic and cardiovascular surgery, 2014

To demonstrate a novel, reproducible, and effective method of direct innominate artery cannulatio... more To demonstrate a novel, reproducible, and effective method of direct innominate artery cannulation using a 14 F pediatric venous cannula to establish antegrade cerebral protection (ACP) in patients undergoing aortic surgery that requires an open distal anastomosis or hemiarch replacement. We reviewed prospectively gathered data on all patients who had undergone replacement of the ascending aorta or hemiarch with an open distal anastomosis using deep hypothermic circulatory arrest and direct innominate artery cannulation with a 14 F pediatric venous cannula at our institution. After central cannulation and cooling to 25 °C to 28 °C, all patients had ACP initiated by way of a direct innominate cannula placed over a guidewire. Fifty patients underwent direct innominate artery cannulation with our technique from 2010 to 2012. The operative mortality was 2% (n = 1), and the rates of neurologic morbidity were acceptable and similar to those with other methods of ACP delivery: stroke (2%, ...

The Canadian journal of cardiology, 2014

This position statement addresses issues in revascularization for multivessel coronary artery dis... more This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life. One purpose of this document is to propose practical multidisciplinary approaches to the management of these patients. Recommendations are made for revascularization in ac...

The Journal of Thoracic and Cardiovascular Surgery, 2011

Recombinant factor VIIa can decrease postoperative bleeding after cardiac surgery. However, the p... more Recombinant factor VIIa can decrease postoperative bleeding after cardiac surgery. However, the potential for recombinant factor VIIa to cause early vascular graft occlusion at the site of new vascular anastomoses has not been fully explored. We hypothesized that recombinant factor VIIa would cause a dose-dependent reduction in vascular graft patency in rabbits. Reversed end-to-end interpositional vein grafts were sutured into the carotid artery of heparinized rabbits, and then recombinant factor VIIa (300 μg/kg, 90 μg/kg, or 20 μg/kg intravenously) or placebo was administered (n = 16/group). Graft patency was assessed at 24 hours using a vascular ultrasound probe. Factor VII activity levels were measured using a prothrombin time-based assay. In different rabbits, the patency of venous end-to-side anastomoses and simple carotid arterial repairs was assessed (recombinant factor VIIa, 300 μg/kg vs placebo, n = 8/group). Data were analyzed using Fisher's exact test, t tests, or analysis of variance. Physiologic variables (activated clotting time, hemoglobin, pH, Pao(2)) and vessel diameter were not different between groups. Vein graft patency was reduced (93.8%, 81.2%, 13.8%, and 6.3%) as factor VII activity levels increased (1.8 ± 0.4, 4.4 ± 2.1, 11.8 ± 4.7, and 23.6 ± 16.9 U/mL, respectively) with increasing doses of recombinant factor VIIa administered (0, 20, 90, and 300 μg/kg, respectively, P < .05). Patency in the arterial repairs and end-to-side venous grafts was also reduced in recombinant factor VIIa-treated rabbits (P < .05 for both). This study suggests that recombinant factor VIIa is associated with a dose-dependent increase in fresh vascular graft occlusion. Higher doses of recombinant factor VIIa may be associated with increased thrombotic outcomes.

The Journal of Thoracic and Cardiovascular Surgery, 2011

Many surgeons consider the tricuspid valve to be a second-class structure. Our objective was to d... more Many surgeons consider the tricuspid valve to be a second-class structure. Our objective was to determine the normal anatomy and dynamic characteristics of the tricuspid valve apparatus in vivo and to discern whether this would aid the design of a tricuspid valve annuloplasty ring model. Sixteen sonomicrometry crystals were placed around the tricuspid annulus, at the bases and tips of the papillary muscles, the free edges of the leaflets, and the right ventricular apex during cardiopulmonary bypass in 5 anesthetized York Hampshire pigs. Animals were studied after weaning of cardiopulmonary bypass on 10 cardiac cycles of normal hemodynamics. Sonomicrometry array localizations demonstrate the multiplanar shape of the tricuspid annulus. The tricuspid annulus reaches its maximum area (97.9 ± 25.4 mm(2)) at the end of diastole and its minimum area (77.3 ± 22.5 mm(2)) at the end of systole, and increases again in early diastole. Papillary muscles shorten by 0.8 to 1.5 mm (11.2%) in systole, and chordae tendineae straighten by 0.8 to 1.7 mm (11.4%) in systole. The shape of the tricuspid annulus is a multiplanar 3-dimensional one with its highest point at the anteroseptal commissure and its lowest point at the posteroseptal commissure, and the anteroposterior commissure is in a middle plane in between. The tricuspid annulus area reaches its maximum during diastole and its minimum during systole. The papillary muscles contract by the same amount of chordal straightening. The optimal tricuspid annuloplasty ring may be a multiplanar 3-dimensional one that mimics the normal tricuspid annulus.

Journal of Cardiothoracic Surgery, 2011

Background: Median sternotomy infection and bony nonunion are two commonly described complication... more Background: Median sternotomy infection and bony nonunion are two commonly described complications which occur in 0.4 -5.1% of cardiac procedures. Although relatively infrequent, these complications can lead to significant morbidity and mortality. The aim of this retrospective study is to evaluate the initial experience of a transverse plate fixation system following wound complications associated with sternal dehiscence with or without infection following cardiac surgery. Methods: A retrospective chart review of 40 consecutive patients who required sternal wound reconstruction post sternotomy was performed. Soft tissue debridement with removal of all compromised tissue was performed. Sternal debridement was carried using ronguers to healthy bleeding bone. All patients underwent sternal fixation using three rib plates combined with a single manubrial plate (Titanium Sternal Fixation System ® , Synthes). Incisions were closed in a layered fashion with the pectoral muscles being advanced to the midline. Data were expressed as mean ± SD, Median (range) or number (%). Statistical analyses were made by using Excel 2003 for Windows (Microsoft, Redmond, WA, USA). Results: There were 40 consecutive patients, 31 males and 9 females. Twenty two patients (55%) were diagnosed with sternal dehiscence alone and 18 patients (45%) with associated wound discharge. Thirty eight patients went on to heal their wounds. Two patients developed recurrent wound infection and required VAC therapy. Both were immunocompromised. Median post-op ICU stay was one day with the median hospital stay of 18 days after plating. Conclusion: Sternal plating appears to be an effective option for the treatment of sternal wound dehiscence associated with sternal instability. Long-term follow-up and further larger studies are needed to address the indications, benefits and complications of sternal plating.

Journal of Cardiothoracic Surgery, 2009

Background: Diffuse microvascular bleeding remains a common problem after cardiac procedures.

JACC: Cardiovascular Interventions, 2008

Objectives The purpose of this study was to compare outcomes for drug-eluting stents (DES) and co... more Objectives The purpose of this study was to compare outcomes for drug-eluting stents (DES) and coronary artery bypass graft (CABG) surgery in patients with unprotected left main coronary artery (ULMCA) stenosis.

Echocardiography, 1985

Albumin is commonly used as a volume expander in cardiopulmonary bypass (CPB) prime. Pentastarch,... more Albumin is commonly used as a volume expander in cardiopulmonary bypass (CPB) prime. Pentastarch, a low molecular weight hetastarch, may provide similar efficacy at decreased cost but is known to alter coagulation profiles. Infectious concerns forced the temporary withdrawal of albumin in our institution. Therefore we evaluated pentastarch as an alternative with regards to perioperative hemostasis and blood loss. One hundred consecutive adult patients undergoing first-time aorto-coronary bypass were given 750 mL of 10% pentastarch (represented as P in calculations) diluted in 1000 mL of Ringer's solution added in their CPB prime. A similar control group of 100 consecutive patients had received 200 mL of 25% albumin (represented as A in calculations) diluted in 1500 mL of Ringer's solution. Postoperative prothrombin time (PT) was slightly higher with pentastarch (P: 14.9 +/- 1.5 seconds, A: 14.2 +/- 1.3 seconds, p = 0.003). Postoperative bleeding was also increased (P: 2337 +/- 1242 mL, A: 1981 +/- 1121 mL, p = 0.034), mostly because of recirculated shed mediastinal blood (P: 834 +/- 499 mL, A: 640 +/- 388, p = 0.002) rather than lost pleural tube blood (P: 1503 +/- 821 mL, A: 1341 +/- 824 mL, p = 0.16). Overall net blood loss (P: 2014 +/- 914 mL, A: 2061 +/- 1015, p = 0.73) was similar. Blood-product transfusion requirements and postoperative daily hematocrits did not differ. The diminished coagulability associated with this dose of pentastarch resulted in increased postoperative bleeding. However, with recirculation of shed mediastinal blood, there was no net increase in blood loss. In this setting, pentastarch may serve as a suitable alternative to albumin.

Canadian Journal of Cardiology, 2010

Myocardial ischemia triggers the expression of multiple angiogenic factors including vascular end... more Myocardial ischemia triggers the expression of multiple angiogenic factors including vascular endothelial growth factor and its receptors. However, vascular endothelial growth factor does not act in isolation. To identify other genes important in the angiogenic response to clinically relevant myocardial ischemia. Paired intraoperative biopsies of ischemic and nonischemic myocardium were obtained from 12 patients with acute coronary syndromes (ACS) undergoing urgent coronary artery bypass graft surgery. Real-time polymerase chain reaction demonstrated significant upregulation of angiopoietin-2 (Ang-2) in ischemic myocardium, to a greater extent than other classical angiogenic factors. Microarray gene profiling identified Ang-2 to be among the top 10 differentially upregulated genes, in addition to genes involved in inflammation, cell signalling, remodelling and apoptosis. The present document is the first report of microarray analysis of patients with ACS, and supports an important role for Ang-2 in the angiogenic response to severe ischemia in the human heart. Common gene expression patterns in ACS may provide opportunities for targeted pharmacological and cellular intervention.

The Annals of Thoracic Surgery, 1996

Infusion of shed mediastinal blood using an autotransfusion system is a widely applied technique ... more Infusion of shed mediastinal blood using an autotransfusion system is a widely applied technique of blood conservation in cardiac surgery. Serial determinations of serum creatine kinase (CK), its MB isoenzyme (CK-MB), and lactate hydrogenase (LDH) levels have been used to monitor perioperative myocardial injury. We investigated the impact of postoperative autotransfused blood infusion on serum levels of these enzymes. We performed a retrospective analysis of postoperative serum CK, CK-MB, and LDH levels of 300 patients who had elective uncomplicated aortocoronary bypass grafting. Shed mediastinal blood samples from 26 patients were analyzed for CK, CK-MB (enzymatic activity and mass), and LDH levels before infusion. High postoperative serum levels of CK and LDH were observed after infusion of autotransfused blood. Shed mediastinal blood contained extremely high levels of these enzymes, particularly from patients who had internal mammary artery dissection. There was a strong correlation (r = 0.96) between measured CK-MB enzyme activities and those calculated from the CK-MB mass units. Infusion of autotransfused blood containing high concentrations of CK and LDH results in elevated serum levels of these enzymes. Hemolysis, frequently present in shed blood, does not interfere with the routine biochemical assays for CK and CK-MB enzyme activities. Caution should be taken when postoperative cardiac enzyme levels are used to determine myocardial injury after aortocoronary bypass grafting if autotransfusion is used as a method of blood conservation.

PLOS ONE, 2015

We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembr... more We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.