Plasma levels, protein binding, and elimination data of lidocaine and active metabolites in cardiac patients of various ages

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110103/1/cptclpt1983122.pd

Coronary artery dissection caused by exit of the guidewire through the distal perfusion sidehole of an auto-perfusion angioplasty balloon catheter

A previously unrecognized cause of coronary artery dissection is reported. A 67-year-old woman underwent angioplasty of the right coronary artery using an autoperfusion balloon catheter. Dissection occurred because the balloon catheter was advanced while the guidewire exited from one of the distal perfusion sideholes. © Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38219/1/1810330109_ftp.pd

The role of the neutrophil and free radicals in ischemic myocardial injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27676/1/0000059.pd

Myocardial glutathione depletion impairs recovery of isolated blood-perfused hearts after global ischaemia

This study was performed to determine whether depletion of myocardial glutathione would impair recovery of left ventricular function of blood-perfused, isolated hearts after reversible ischaemic injury. Cats were treated with either vehicle or buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the synthesis of glutathione. The feline isolated hearts were perfused with the blood of normal donor cats before and after 40 min of global myocardial ischaemia. The myocardial concentration of glutathione of the BSO group, 178+/-38 ng/mg tissue, was significantly less than that of the control group, 292+/-38 ng/mg tissue (PP=0.05 vs. control). The peak left ventricular dP/dt after reperfusion, expressed as a fraction of the peak dP/dt before ischaemia, was 1.08+/-0.14 for the control group and 0.78+/-0.09 for the BSO group (P=0.05 vs. control). The myocardial creatine kinase activity of the BSO group, 1046+/-46 U/g tissue, was not significantly different from that of the control group, 1038+/-17 U/g tissue (P=0.87). Thus, depletion of myocardial glutathione resulted in impaired post-ischaemic contractile function that cannot be attributed to a greater extent of irreversible cell injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29775/1/0000114.pd

Myocardial ischemia and reperfusion: The role of oxygen radicals in tissue injury

Thrombolytic therapy has gained widespread acceplance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B 4 and C 5a , which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE 1 ), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury. Current data are highly suggestive of a deleterious role of the neutrophil in organ reperfusion and justify consideration of the clinical investigation of neutrophil inhibitors in patients receiving thrombolytic agents during the evolution of an acute myocardial infarction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44595/1/10557_2004_Article_BF00133206.pd

Effect of ACE inhibitors on endothelial dysfunction: Unanswered questions and implications for further investigation and therapy

Experimental studies have suggested that angiotensin-converting enzyme (ACE) inhibitors may have an important role in blocking the progression of and/or reversing endothelial dysfunction. The extrapolation of these experimental studies to the clinical situation has, however, been disappointing. Studies of forearm-mediated endothelial vasodilatation in patients with hypertension with captopril, enalapril, and cilazapril have been negative. The finding of the Trial in Reversing Endothelial Dysfunction (TREND) that the administration of quinapril to normotensive patients with coronary artery disease in part restores endothelial-mediated coronary vasodilation, as assessed by intracoronary administration of acetylcholine, has important implications for future therapy and raises several important questions. The differences in the TREND and previous studies of ACE inhibitors on endothelial dysfunction may be due to mechanistic differences in endothelial dysfunction in patients with coronary artery disease and hypertension. Although in general there has been a good correlation between endothelial dysfunction as assessed by forearm flow and coronary endothelial dysfunction as assessed by acetylcholine, these vascular beds may be affected differently by therapeutic interventions, especially with an ACE inhibitor, which may affect sheart stress and angiotensin II formation in different vascular beds differently. Third, one needs to question whether the effect of quinapril on coronary endothelial dysfunction is a class effect or unique to quinapril. It will be necessary to test the effectiveness of other ACE inhibitors on coronary endothelial dysfunction in humans before concluding that the beneficial effects of quinapril are due to a class effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44542/1/10557_2004_Article_BF00051113.pd

Lethal Myocardial Reperfusion Injury: Fact or Fiction?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48014/1/11239_2004_Article_255434.pd

Leukocytes, oxygen radicals, and myocardial injury due to ischemia and reperfusion

Ischemic myocardium generates stimuli for neutrophil chemotaxis before the final extent of irreversible ischemic injury is attained. Reperfusion accelerates the infiltration of ischemic myocardium by neutrophils. Oxygen radicals released by the activated neutrophils may exacerbate the tissue damage caused by ischemia. Neutrophil depletion by antiserum was shown to limit infarct size in dogs undergoing coronary occlusion for 90 minutes followed by reperfusion for 6 or 72 hours, but not in dogs undergoing occlusion for 4 hours. Prostacyclin, which inhibits the generation of superoxide anions by neutrophils, also limited canine myocardial injury despite no effect on collateral blood flow. Iloprost, an analogue of prostacyclin that inhibits neutrophils also reduced infacrt size, while SC39902, an analogue that does not inhibit neutrophils, did not alter infarct size. The results suggest that oxygen radicals released by activated neutrophils play a role in the pathophysiology of myocardial injury due to ischemia followed by reperfusion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27448/1/0000488.pd