Richard D. Weisel

C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function Further Evidence of a Mechanistic Link Between C-Reactive Protein and Cardiovascular Disease

Background—Myocardial ischemia provides a potent stimulus to angiogenesis, and the mobilization and differentiation of endothelial progenitor cells (EPCs) has been shown to be important in this process. An elevated level of C-reactive protein (CRP) has emerged as one of the most powerful predictors of cardiovascular disease. However, the impact of CRP on EPC biology is unknown. Methods and Results—EPCs were isolated from the peripheral venous blood of healthy male volunteers. Cells were cultured in endothelial cell basal medium-2 in the absence and presence of CRP (5 to 20 μg/mL), rosiglitazone (1 μmol/L), and/or vascular endothelial growth factor. EPC differentiation, survival, and function were assayed. CRP at concentrations ≥15 μg/mL significantly reduced EPC cell number, inhibited the expression of the endothelial cell–specific markers Tie-2, EC-lectin, and VE-cadherin, significantly increased EPC apoptosis, and impaired EPC-induced angiogenesis. EPC-induced angiogenesis was dependent on the presence of nitric oxide, and CRP treatment caused a decrease in endothelial nitric oxide synthase mRNA expression by EPCs. However, all of these detrimental CRP-mediated effects on EPCs were attenuated by pretreatment with rosiglitazone, a peroxisome proliferator–activated receptor-γ (PPARγ ) agonist. Conclusions—Human recombinant CRP, at concentrations known to predict adverse vascular outcomes, directly inhibits EPC differentiation, survival, and function, key components of angiogenesis and the response to chronic ischemia. This occurs in part via an effect of CRP to reduce EPC eNOS expression. The PPARγ agonist rosiglitazone inhibits the negative effects of CRP on EPC biology. The ability of CRP to inhibit EPC differentiation and survival may represent an important mechanism that further links inflammation to cardiovascular disease.

Should Radial Arteries Be Used Routinely for Coronary Artery Bypass Grafting

Case Presentation : Mr P is a 57-year-old construction worker who has had Canadian Cardiovascular Society class III angina for the past 3 months. He has multiple cardiovascular risk factors including smoking, hypertension, dyslipidemia, and diabetes. He is obese and has had a previous laparotomy for a perforated bowel. Coronary angiography revealed triple vessel disease involving the left anterior descending artery (LAD), the first obtuse marginal branch, and the right coronary artery (RCA), and an akinetic inferior wall with an estimated ejection fraction of 40%. The patient was referred for consideration of coronary artery bypass graft (CABG) surgery. Is Mr P a candidate for CABG and, if so, which vascular conduits should be used?nnCABG is the standard surgical procedure for the treatment of advanced coronary artery disease. Since the first successful results reported by Favaloro,1 CABG surgery has been demonstrated to improve symptoms and, in specific subgroups of patients, to prolong life.2 Despite its success, the long-term outcome of coronary bypass surgery is strongly influenced by the fate of the vascular conduits used. Five to 7 years after surgery, patients are at increased risk of suffering from ischemic complications coincident with graft failure.2 Furthermore, as patients undergoing CABG surgery become older with more preoperative risk factors, and treated patients are living longer and therefore requiring reoperation, the optimal selection of vascular grafts for bypass is essential.nnConventional CABG surgery utilizes a combination of arterial and venous grafts. Saphenous vein (SV) grafts, the first vascular conduits used in CABG, are still widely utilized, primarily to bypass vessels other than the LAD. Despite being readily accessible, of adequate length to access every vessel on the heart, and the correct diameter to facilitate coronary and aortic anastomoses, SV grafts are limited by poor long-term patency. Because of a combination …

Off-Pump Coronary Artery Bypass Surgery Fundamentals for the Clinical Cardiologist

Case Report: Mrs. G is a 65-year-old retired banker who has had Canadian Cardiovascular Society class III angina for the past 2 months and symptomatic intermittent claudication for the past year. Her past medical history is unremarkable except for the presence of multiple vascular risk factors (smoking, hypertension, dyslipidemia, and diabetes). Coronary angiography revealed triple vessel disease involving the left anterior descending, second obtuse marginal, and right coronary arteries, as well as the akinetic anterior and inferior walls, with an estimated ejection fraction of 30%. Carotid duplex revealed 40% stenosis of the right internal carotid artery and 60% stenosis of the left internal carotid artery. A chest x-ray showed a possible calcified ascending aorta. The patient was referred for consideration of coronary artery bypass graft (CABG) surgery. Is Mrs. G a candidate for off-pump CABG? What are the indications, precautions, and considerations that facilitate decision-making about off-pump CABG surgery?nnConventional CABG surgery uses cardiopulmonary bypass (CPB) to allow cardiac surgeons to operate on a motionless heart that has been arrested by means of cardioplegia. CABG with CPB (on-pump CABG) quickly became the gold standard surgical procedure for myocardial revascularization, as it allowed surgeons to bypass multiple coronary arteries with greater control and precision. However, recently there has been increasing interest in the development and use of technologies that allow surgeons to perform CABG surgery without CPB (known as off-pump CABG or OPCAB).nnCPB is not a benign intervention. It is associated with a number of adverse consequences that are primarily related to a systemic inflammatory response elicited by the activation of cellular and humoral mediators as circulating blood comes into contact with the extracorporeal circuit of the CPB machine. The biochemical, cellular, and molecular aspects of this pump-induced inflammatory response are believed to contribute to postoperative myocardial, renal, and neurological …

Is atrial function affected by conventional cardioplegic arrest

Conventional cardioplegic arrest results in persistent atrial electrical and mechanical activity. This activity has been postulated to result in atrial ischemia which can induce postoperative arrhythmias and impair the transport function of the atrium. In this study, the effects of simple cardiopulmonary bypass (CPB) (seven pigs) and conventional cardioplegic arrest (CCA) (seven pigs) on right atrial function were evaluated. Function was assessed in an isolated right atrial preparation with a compliant balloon inserted via the superior vena cava. CCA for 1 hr produced significant deterioration in right atrial function (developed pressure 14.1 +/- 0.7 vs 18.9 +/- 0.8 mm Hg, P less than 0.05, diastolic pressure 10.0 +/- 1 vs 4.5 +/- 1.4 mm Hg, P less than 0.05, dP/dt 134 +/- 25 vs 187 +/- 19 mm Hg/sec, P less than 0.05 at a balloon volume of 20 ml after 1 hr of reperfusion). CPB alone caused no alteration in pressures in the right atrium but was associated with a late decrease in dP/dt (developed pressure 19.3 +/- 1.8 vs 18.9 +/- 0.8 mm Hg, diastolic pressure 4.0 +/- 1.2 vs 4.5 +/- 1.4 mm Hg, dP/dt 148 +/- 18 vs 187 +/- 19, P less than 0.05 at a balloon volume of 20 ml at a time corresponding to 1 hr of reperfusion in the CCA group). These results are consistent with the postulate that conventional techniques of cardioplegic arrest are associated with ischemic dysfunction of the right atrium.