Nikola Dobrilovic

Changes in Microvascular Reactivity after Cardiopulmonary Bypass in Patients with Poorly Controlled versus Controlled Diabetes

Background— We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched nondiabetic (ND) patients undergoing coronary artery bypass grafting (CABG). Methods and Results— Skeletal muscle arterioles were harvested before and after CPB from the UDM patients (hemoglobin A1c [HbA1c]=9.0±0.3), the CDM patients (HbA1c=6.3±0.15), and the ND patients (HbA1c=5.2±0.1) undergoing CABG surgery (n=10/group). In vitro relaxation responses of precontracted arterioles to endothelium-dependent vasodilators adenosine 5′-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P, and SNP of arterioles from the UDM patients were decreased as compared with microvessels from the ND or CDM patients (P<0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all 3 groups compared with pre-CPB responses (P<0.05). However, these decreases were more pronounced in the UDM group (P<0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other 2 groups compared with pre-CPB. The expression of protein kinase C (PKC)-&agr;, PKC-&bgr;, protein oxidation, and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (P<0.05). Conclusions— Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-&agr; and PKC-&bgr; and enhanced oxidative and nitrosative stress.

Altered Apoptosis-Related Signaling After Cardioplegic Arrest in Patients With Uncontrolled Type 2 Diabetes Mellitus

Background— We investigated the effects of cardioplegic arrest and reperfusion (CP/Rep) on myocardial apoptosis and key apoptotic mediators, such as apoptosis-inducing factor, caspase 3, caspase 8, caspase 9, poly(adenosine diphosphate-ribose) polymerase, B-cell lymphoma 2 (Bcl-2) family proteins, and protein kinase C (PKC), in uncontrolled type 2 diabetic, controlled type 2 diabetic, and nondiabetic patients. Methods and Results— Right atrial tissue was harvested pre- and post-CP/Rep from uncontrolled type 2 diabetic patients (hemoglobin A1c=9.6±0.25), controlled type 2 diabetic patients (hemoglobin A1c=6.5±0.15), and nondiabetic patients (hemoglobin A1c=5.4±0.12) undergoing coronary artery bypass grafting (n=8/group). Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was used for the identification of apoptotic cells. Total and modified apoptosis-inducing factor, Bcl-2 family proteins, phospho-PKC-&agr;, phospho-PKC-&bgr;1, and poly(adenosine diphosphate-ribose) polymerase were quantified by immunoblotting or immunohistochemistry. At baseline, the number of apoptotic cells and expression of total apoptosis-inducing factor, Bcl-2, Bak, and Bax in the pre-CP/Rep atrial tissue from uncontrolled type 2 diabetic patients were significantly increased compared with those of nondiabetic or controlled type 2 diabetic patients (P<0.05). After CP/Rep, the amount of apoptotic cells, apoptosis-inducing factor, phospho-Bad, phospho-PKC-&agr;, phospho-PKC-&bgr;1, and cleaved poly(adenosine diphosphate-ribose) polymerase in post-CP/Rep atrial tissue were increased in all 3 groups compared with pre-CP/Rep. These increases after CP/Rep were more pronounced in the uncontrolled type 2 diabetic group. In addition, there were significant increases in the expression of cleaved caspase 8 and caspase 9 in the basal and post-CP/Rep atrium of uncontrolled type 2 diabetic group compared with nondiabetic or controlled type 2 diabetic group. Conclusions— Uncontrolled diabetes mellitus is associated with increases in myocardial apoptosis and expression of key apoptosis mediators at baseline and in the setting of CP/Rep.

Midterm outcomes of patients undergoing aortic valve replacement after previous coronary artery bypass grafting

OBJECTIVES Redo cardiac surgery for aortic valve replacement (AVR) after previous coronary artery bypass grafting (CABG) is technically challenging and carries a high incidence of peri-operative complications. However, experience in the field continues to evolve generating reproducible, and increasingly safer results. We anticipate an increased future role for catheter-based valve procedures and review our operative results to maintain current surgical outcomes for comparison. METHODS A retrospective review was conducted from 1996 through 2010 of patients undergoing AVR as a re-operation after previous CABG. Data were obtained through query of the Society of Thoracic Surgeons (STS) database and chart review. Patient outcomes were compared with STS-predicted risk scores. RESULTS One hundred and thirty-two patients met inclusion criteria (male 83%, female 17%). Average age was 76 (± 7). Thirty-seven patients (28%) required concomitant CABG. Average ejection fraction was 45 (± 14). Comorbid conditions included: diabetes 37% (49/132), hypertension 87% (115/132), NYHA class III/IV 83% (110/132), smoking 51% (67/132), chronic obstructive pulmonary disease 21% (27/132), history of myocardial infarction 61% (80/132), renal failure 16% (21/132) and peripheral arterial disease 38% (50/132).Operative (30-day + hospital) mortality was 6.1% (8/132; 95% CI = 2.9-12.0%), and 30-day mortality was 3.8% (5/132; 95% CI = 1.4-9.1%). One, three and five-year survival rates were 86, 74 and 62%, respectively. Complication rates were as follows: re-operation for bleeding 2.3% (3/132), permanent stroke 0.8% (1/132), prolonged ventilator requirement 18.2% (24/132), deep sternal wound infection 0% (0/132; CI = 0.0-3.5%) and renal failure 9.1% (12/132; none required dialysis). The mean STS-predicted mortality risk score was 7.8% for 111 (applicable) patients for whom actual operative (30-day + hospital) mortality was 3.6%. CONCLUSIONS Low initial operative mortality suggests that surgery is safe and reproducible. However, older age and multiple comorbidities in this patient population may significantly influence late outcomes. The data reported in this study: (i) support open surgical technique as a safe, reliable approach for redo AVR in patients who have undergone previous CABG, and (ii) add to the large body of evidence suggesting that STS scores overestimate risk.

Altered expression and activation of mitogen-activated protein kinases in diabetic heart during cardioplegic arrest and cardiopulmonary bypass

BACKGROUND We investigated whether mitogen-activated protein kinases (MAPKs) are changed in the hearts of patients with diabetes after cardioplegia and cardiopulmonary bypass (CP/CPB) operations. METHODS Biopsies from the right atrial appendage were harvested pre- and post-CP/CPB from nondiabetic (ND) patients (n = 8, hemoglobin A1c (HbA1c) = 5.4 ± 0.12); patients with controlled diabetes (CDM) (n = 8, HbA1c = 6.5 ± 0.15); and patients with uncontrolled diabetes (UDM) (n = 8, HbA1c = 9.6 ± 0.3) undergoing coronary artery bypass grafting. The expression and/or activation of the p38-MAPK, ERK1/2, JNK, and MKP-1 in the right-atrial tissues were analyzed by Western blotting. The vasomotor function of coronary arterioles was measured by videomicroscopy. RESULTS The post-CP/CPB levels of total p38-MAPK were decreased in the 3 groups as compared with their pre-CP/CPB levels (P < .05). There were increases in phospho-p38-MAPK, phospho-ERK1/2, and MKP-1 in UDM patients as compared with ND and CDM patients at baseline (P < .05). Compared to pre-CP/CPB, the post-CP/CPB levels of phospho-p38-MAPK decreased in the UDM group but were unaltered in the ND and CDM groups; however, the post-CP/CPB levels of phospho-p38-MAPK still remained greater than the post-CP/CPB levels of the other 2 groups. Post-CP/CPB levels of phospho-ERK1/2 were increased in the ND and CDM groups but were decreased in the UDM group compared to their pre-CP/CPB levels, respectively (P < .05). There were no significant differences in phospho-JNK in 3 groups at baseline. Post-CP/CPB levels of phospho-JNK, however, were increased in the 3 groups and were more pronounced in the myocardium of the UDM group (P < .05). After CP/CPB, the protein levels of MKP-1 were unchanged in the 3 groups when compared with their pre-CP/CPB levels. Post-CP/CPB levels of MKP-1, however, remained greater in the UDM group than in the ND and CDM groups. The post-CP/CPB contractile responses to the thromboxane A2 analog U46619 were significantly impaired in all 3 groups compared with pre-CP/CPB contractile responses. These impairments were more pronounced in the UDM group. CONCLUSION Uncontrolled diabetes is associated with changes in expression of and activation of MAPKs and vasomotor dysfunction in the setting of CP/CPB.

Impaired contractile response of human peripheral arterioles to thromboxane A-2 after cardiopulmonary bypass.

BACKGROUND We studied the contractile response of human peripheral microvasculature to thromboxane A-2 (TXA-2) before and after cardiopulmonary bypass (CPB), with and without the blockade of TXA-2 receptors, or the inhibition of phospholipase C (PLC), phospholipase A-2 (PLA-2) or protein kinase C (PKC)-α. We also examined the protein/gene expression and localization of TXA-2 receptors, TXA-2 synthase, PLC, and other TXA-2-related proteins. METHODS Skeletal muscle arterioles (90-180 μm in diameter) were harvested pre- and post-CPB from patients (n = 28) undergoing cardiac surgery. RESULTS The post-CPB contractile response of skeletal muscle arterioles to TXA-2 analog U-46619 was impaired compared with pre-CPB (P < .05). The presence of TXA-2 receptor antagonist SQ-29548 (10(-6)mol/L) prevented the contractile response to U-46619 (P < .05). Pretreatment with the PLC inhibitor U-73122 (10(-6)mol/L) significantly inhibited the U-46619-induced contractile response (P < .01). Administration of the PLA-2 inhibitor quinacrine (10(-6)mol/L) or PKC-α inhibitor safingol (2 × 10(-5)mol/L), however, failed to affect U-46619-induced contraction. Total protein levels and gene expression of TXA-2 receptors, and TXA-2 synthase of skeletal muscle, were not altered post-CPB. Confocal microscopy showed no differences in the expression of PLCβ-3 in the microcirculation. PLCβ-3 was localized to both smooth muscle and endothelium. CONCLUSION CPB decreases the contractile response of human peripheral arterioles to TXA-2 soon after cardiac surgery. This response may be in part responsible for the decrease in vascular tone, and accompanying hypotension sometimes observed after cardiac operations utilizing CPB.

The influence of seasons and lunar cycle on hospital outcomes following ascending aortic dissection repair

OBJECTIVES The effect of the lunar cycle and seasonal variation on ascending aortic dissection surgery outcomes is unknown. We investigated these temporal effects on risk-adjusted hospital mortality and then on the length of stay (LOS) following surgery for survivors. METHODS We examined prospectively collected data from cardiac operations at two major centres within a single state between January 1996 and December 2011. We first examined the relationship between the lunar cycle and seasonal variation, along with demographic and risk profile covariates, with mortality using univariate analyses, followed by multiple logistic regression modelling that controlled for demographic and patient risk variables including age, gender, risk profile (diabetes, hypertension, dyslipidaemia and renal failure), and two surgical groups: Group A, consisting of patients having repair of ascending aorta dissection repair only, and Group B, with those having ascending aorta repair plus aortic valve surgery or coronary bypass surgery or both. We further examined the relationship with LOS using both univariate and multiple regression analyses. RESULTS There were 210 patients who had repair of dissection in the study period, with 109 patients in Group A and 101 in Group B. The average age of this sample was 59.5 (standard deviation = 16.0), 65.7% were male and 18.1% died prior to discharge following repair. The greatest percentage of deaths occurred in winter (31.6%, n = 12), while the least were in summer (21.1%, n = 8) and fall (21.1%, n = 8). An overall χ(2) test found there was no difference in mortality for season (P = 0.55). Univariate analyses also found the age of patients who died vs lived was significantly higher (65.9 vs 58.1 years; P = 0.001), and a significantly greater (P = 0.029) percentage of patients with diabetes vs without diabetes died (41.7 vs 16.7%). Univariate analyses found all other covariates were not significantly related to mortality. In the multiple logistic regression model, there was no significant effect for season, while the odds of dying increased with age (odds ratio [OR] = 1.04, 95% confidence interval [95% CI] = 1.01-1.07, P = 0.012), and the odds of dying in the full-moon cycle vs the new moon cycle was significantly reduced (OR = 0.21, 95% CI = 0.05-0.81, P = 0.024). No other covariate significantly increased or decreased the odds of death, including diabetes risk, which had been significantly related to death in the univariate analysis. Within a linear regression model that examined the relationship with LOS, Group B (P = 0.020), male sex (P = 0.036) and the full-moon lunar phase (P = 0.001) were significantly related to shorter LOS. CONCLUSIONS Season had no effect on mortality or LOS following aortic dissection repair, while patient age significantly increased the odds of death. The full-moon cycle appeared to reduce the odds of death, and the full-moon cycle, along with being male and requiring a concomitant cardiac procedure, was associated with shorter LOS.

Off-pump right atrial surgery: Vena caval inflow occlusion in cardiac lesions

Background Vena caval inflow occlusion, despite its utility in pediatrics, is rarely used in adults. We report the use of inflow occlusion in adults when cardiopulmonary bypass is contraindicated. Methods Between January 1999 and July 2014, 35 patients in 3 hospitals presented with right-sided cardiac lesions; 27 had right-sided endocarditis with sepsis despite maximal medical therapy, the rest had organized sterile masses with embolic potential in the right side of the heart. Comorbidities included immunosuppression, malignancy, and dialysis-dependent renal failure. Twelve patients had heparin-induced thrombocytopenia. Using inflow occlusion on a beating heart, tricuspid valve vegetectomy was performed in 23 patients, vegetectomy and tricuspid valve repair in 3, removal of infected pacing leads in 7, and removal of a migrated inferior vena cava filter in 1. Eight patients had a single 2-min period of vena caval inflow occlusion, and 25 had additional periods of vena caval inflow occlusion after periods of reperfusion. The first 23 procedures were performed through a sternotomy. Nine patients underwent a right minithoracotomy (redo in 2). Results There were no deaths. Infected patients had resolution of sepsis and improvement in respiratory status. Three patients had moderate tricuspid regurgitation, the rest had trivial to mild tricuspid regurgitation. One patient had a transient neurological deficit postoperatively, and one had late empyema. Conclusion Removal of infective material, sterile masses, and retained foreign bodies can safely be performed under vena caval inflow occlusion when cardiopulmonary bypass is contraindicated.

Left Thoracotomy Approach for Implantation of the Abiomed Left Ventricular Assist Device

Abstract  We describe a left thoracotomy approach for implantation of the Abiomed AB5000 left ventricular assist device (LVAD). The technique is easily performed and spares the patient a sternotomy in anticipation of future transplantation or LVAD exchange. (J Card Surg 2012;27:395‐396)

Early complications of biologic extracellular matrix patch after use for femoral artery repair

Background: The CorMatrix (CorMatrix Cardiovascular, Roswell, Ga) biologic extracellular patch derived from porcine small intestinal mucosa provides a biologic scaffold for cellular ingrowth and eventual tissue regeneration. It has been used in a variety of applications, including cardiac and vascular repair procedures. Methods: CorMatrix was used as a patch arterioplasty for femoral artery repair in conjunction with endarterectomy for seven separate procedures in six patients (one patient underwent staged, bilateral femoral procedures). Results: Patients were a median age of 67 years (interquartile range, 3.6 years). Six of seven procedures (86%) were performed on male patients. There were no operative deaths. Three of seven procedures (43%) resulted in significant early complications. Two procedures (29%) resulted in catastrophic biologic extracellular matrix patch disruption (11 and 19 days after initial procedure), requiring emergency exploration, patch removal, and definitive repair with vein patch arterioplasty. Both patches demonstrated an absence of growth on culture. One procedure (14%) resulted in groin pseudoaneurysm formation. Use of the CorMatrix patch was suspended upon recognition of significant complications. Conclusions: Use of CorMatrix patch in the femoral artery position demonstrates a high incidence of early postoperative complications, including catastrophic patch disruption and pseudoaneurysm formation.

Delayed Retrograde Ascending Aortic Dissection After Endovascular Repair of Descending Dissection

We report the case of a 34-year-old woman who developed delayed retrograde ascending aortic dissection after previous endovascular repair of her descending thoracic aorta. Preoperative computed tomography imaging specifically highlights the interaction of endograft springs with the dissection flap and surrounding aortic tissues. Intraoperative findings are presented for comparison and further discussion.