Thrombin in Myocardial Ischemia-Reperfusion During Cardiac Surgery

Raivio, Peter; Lassila, Riitta; Petäjä, Jari

doi:10.1016/j.athoracsur.2008.12.097

Cited by 29 publications

(33 citation statements)

References 92 publications

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“…Although thrombin is considered to be the "gold standard" for platelet activation, many of the principal actions of thrombin may be harmful to the heart. Thrombin is a multifunctional protease, which is pro-apoptotic and pro-inflammatory [28] and may have adverse effects on cardiac myocytes, which are independent of its pro-coagulant activity [28,29]. It has been shown that in humans, thrombin generation during reperfusion after coronary artery bypass surgery is associated with postoperative myocardial damage [30,31] and that its thrombotic activity is only partially suppressed by heparin [29].…”

Section: Discussionmentioning

confidence: 99%

Autologous Platelet Rich Plasma (Platelet Gel): An Appropriate Intervention for Salvaging Cardiac Myocytes under Oxidative Stress after Myocardial Infarction

Hargrave¹

2013

Anat Physiol

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SummaryPlatelet gel improves left ventricular mechanical function in the ischemic reperfused Langendorff rabbit heart, decreases ROS production and mitochondrial depolarization in HUV-EC cells (Homo sapiens, human Umbilical Vein Endothelium) in vitro, protects catalase and superoxide dismutase when prepared using nanosecond pulsed electric fields rather than bovine thrombin and decreases the metalloproteinase MMP-2 and increases the metalloproteinase inhibitor TIMP-1 in H9c2 cells (Rattus norvegicus H9c2 cardiac myoblast cells) in vitro. IntroductionIn patients admitted to a hospital with myocardial infarction, some of the myocardial tissue is irreversibly damaged by necrosis, but a larger part is under ischemic stress and may still be saved by appropriate intervention. It is essential to restore coronary flow to the ischemic region (reperfusion), but if no additional measures are taken, reperfusion causes the production of reactive oxygen species (ROS), which can lead to substantial tissue death (reperfusion injury) [1].Autologous Platelet-rich plasma (PRP) or platelet gel is emerging as a biological tool to reduce cardiovascular reperfusion injury in animal experiments [2]. PRP is made from an animal's own whole blood (autologous). The platelets are concentrated and the release of growth factors from the platelets is induced, typically by combining the platelet concentrate with bovine thrombin and calcium. The resulting "activated" PRP contains a super-physiological concentration of growth factors, cytokines, and other proteins [3]. Injecting it into the myocardium after infarction and prior to reperfusion significantly improves left ventricular mechanical function during reperfusion in vivo [4] in rabbit hearts and promotes angiogenesis and mitogenesis in the sheep heart when injected 3 weeks after coronary ligation and evaluated 9 weeks later [5]. In addition to the growth and healing promoting proteins, PRP provides a scaffold that traps cells such as stem cells in the region of injury giving the proteins time to help the cells differentiate into cardiac myocytes. Several problems have so far precluded the use of activated PRP in the cardiovascular system of patients: 1) injecting a PRP that contains red blood cells into the heart may lead to thrombi that can cause stroke or myocardial infarction; 2) thrombin used to prepare PRP can cause serious bleeding abnormalities in some patients who develop antibodies against certain clotting factors as well as other adverse events 3 (thrombin, itself, causes the generation of ROS and 4) lack of a mechanism explaining the mode of action of activated PRP. AbstractBackground: The prompt restoration of blood flow (reperfusion) to the ischemic myocardium after an acute myocardial infarction is critical to the survival of non damaged heart tissue. However, reperfusion is responsible for additional myocardial damage. Our objective was to investigate the role of autologous platelet rich plasma or platelet gel prepared using nanosecond pulsed electric fields (nsPEFs) in imp...

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Section: Discussionmentioning

confidence: 99%

Autologous Platelet Rich Plasma (Platelet Gel): An Appropriate Intervention for Salvaging Cardiac Myocytes under Oxidative Stress after Myocardial Infarction

Hargrave¹

2013

Anat Physiol

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“…10 In contrast to the results of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, 10 in which bivalirudin use rather than heparin plus a GPI in patients with STEMI resulted in a substantial reduction in cardiac and all-cause mortality, the present analysis of patients with NSTEMI did not demonstrate a beneficial effect of bivalirudin on 30-day mortality after PCI. Although the reasons for this difference are unknown, it is well established that thrombin is an important mediator of ischemia-reperfusion injury, 23 and that antithrombin substances attenuate ischemia-reperfusion injury in experimental models. [24][25][26] Thus, attenuation of reperfusion injury by thrombin inhibition in patients with STEMI may be another beneficial effect of bivalirudin therapy (in addition to its antiplatelet and anticoagulant effects in these patients).…”

Section: Discussionmentioning

confidence: 99%

Bivalirudin Versus Heparin Plus a Glycoprotein IIb/IIIa Inhibitor in Patients With Non–ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment

Ndrepepa

Neumann

Deliargyris

et al. 2012

Circ: Cardiovascular Interventions

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N on-ST-segment elevation acute coronary syndromes (ACS) account for approximately two thirds of patients with ACS.1 Patients with biomarker-positive non-ST-segment elevation myocardial infarction (NSTEMI) represent a highrisk group that differs from biomarker-negative ACS patients with regard to benefit from invasive treatment 2 or type of antithrombotic therapy 3 and prognosis. 4 An early invasive strategy of coronary angiography and revascularization when appropriate improved the outcomes of patients with non-ST-segment elevation ACS. 2,5,6 Over the last decades much research effort has been devoted to finding the most appropriate peri-PCI and maintenance antithrombotic therapy. In Background-The optimal antithrombotic therapy for patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention is not well defined. We investigated the efficacy and safety of bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. Methods and Results-This study included 3798 clopidogrel-pretreated patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, who were randomly assigned to receive bivalirudin (n=1928) or heparin (unfractionated heparin or enoxaparin; n=1870) plus a GPI in the setting of the Acute Catheterization

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“…The filling pressures of patients with high preoperative F1+2 and comparison patients, as well as the filling pressures of patients with low preoperative protein S and comparison patients, were comparable throughout the study (repeated measures ANOVA p=0.81 and p=0.24, respectively, data shown for CVP, Figures 3A and 3B, respectively). There were no differences in the requirement of vasoactive infusions (epinephrine, norepinephrine, or milrinone) during any time point after CPB (time points [2][3][4][5], either between patients in the highest decile of preoperative F1+2 and comparison patients (Fisher's exact test, p≥0.12) or between patients in the lowest decile of preoperative protein S and patients with higher protein S levels (Fisher's exact test, p>0.2).…”

Section: F1+2 Protein S and Hemodynamic Performance After Cpbmentioning

confidence: 95%

“…Several lines of experimental evidence have established thrombin as a mediator of myocardial ischemiareperfusion injury 3 . Recent clinical studies have also demonstrated that the generation of thrombin during coronary artery bypass grafting (CABG) was associated with postoperative myocardial damage 4 and postoperative hemodynamic recovery 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting

et al. 2010

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In a previous study, preoperative levels of activated protein C (APC) were associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the cofactor of activated protein C, has activated protein C-independent anticoagulant activity and cytoprotective effects. Therefore, the objective of this study was to test whether preoperative, baseline levels of either thrombin or protein S were associated with hemodynamic performance or markers of myocardial damage after CABG. One hundred patients undergoing elective on-pump CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin generation) and free protein S were measured preoperatively and cardiac index, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were measured serially thereafter at fixed time points. Cardiac biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse correlation between preoperative F1+2 and free protein S levels (r= -0.30, p=0.003). High preoperative F1+2 and low preoperative protein S levels were associated with a less favorable hemodynamic profile postoperatively. Patients with F1+2 in the highest decile (≥0.85 nmol/l) and patients with preoperative protein S in the lowest decile (≤63%) had lower CI values, and higher pulmonary and systemic vascular resistance index values postoperatively than comparison patients. Preoperative F1+2 or protein S did not correlate with postoperative cardiac biomarker levels. Baseline activation of coagulation and the balance between pro-coagulant and anti-coagulant factors preoperatively might have implications for postoperative hemodynamic recovery after CABG.

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Thrombin in Myocardial Ischemia-Reperfusion During Cardiac Surgery

Cited by 29 publications

References 92 publications

Autologous Platelet Rich Plasma (Platelet Gel): An Appropriate Intervention for Salvaging Cardiac Myocytes under Oxidative Stress after Myocardial Infarction

Autologous Platelet Rich Plasma (Platelet Gel): An Appropriate Intervention for Salvaging Cardiac Myocytes under Oxidative Stress after Myocardial Infarction

Bivalirudin Versus Heparin Plus a Glycoprotein IIb/IIIa Inhibitor in Patients With Non–ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment

Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting

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