Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart

The aim of this study was to assess the effect of two differentcalcium channel blockers on myocardial blood flow and functionin a rat model of myocardial ‘stunning’ by repeatedshort episodes of ischaemia (‘repetitive ischaemia’).In an open chest rat model, the left anterior descending coronaryartery was ligatedfor 10 mm followed by 15 min reperfusion.In total, five periods of ischaemia and reperfusion were performed.Myocardial blood flow was assessed by the hydrogen clearancetechnique and systolic thickening fraction by pulsed Doppler.After five episodes of ischaemia, myocardial blood flow andmyocardial thickening in the ischaemic area were reduced by60±8% and 52±7% (n=9), respectively, as comparedto baseline. Continuous intravenous infusion of the calciumchannel blockers nifedipine (n=6) and gallopamil (n=6), started20 min prior to onset of ischaemia, attenuated the ischaemia-induceddecrease of myocardial perfusion. Nifedipine was the most effectivewith only 5±2% reduction in blood flow after five ischaemicepisodes, whereas reduction of myocardial blood flow was 30±4%in the presence of gallopamil. However, neither nifedipine norgallopamil were able to prevent regional ventricular dysfunctioninduced by repetitive ischaemia. Despite the preservation ofmyocardial blood flow following repetitive ischaemia, calciumchannel blockers do not prevent ischaemia-induced reductionof myocardial function in the ischaemic area.     

Autoantibodies to heat shock protein 60 promote thrombus formation in a murine model of arterial thrombosis

Summary. Background and objectives: Anti‐heat shock protein (HSP)60 autoantibodies are associated with atherosclerosis and are known to affect endothelial cells in vitro. However, their role in thrombus formation remains unclear. We hypothesized that anti‐HSP60 autoantibodies could potentiate thrombosis, and evaluated the effect of anti‐murine HSP60 antibodies in a ferric chloride (FeCl₃)‐induced murine model of carotid artery injury. Methods: Anti‐HSP60, or control, IgG was administered to BALB/c mice 48 h prior to inducing carotid artery injury, and blood flow was monitored using an ultrasound probe. Results: Thrombus formation was more rapid and stable in anti‐HSP60 IGG‐treated mice than in controls (blood flow = 1.7% ± 0.6% vs. 34% ± 12.6%, P = 0.0157). Occlusion was complete in all anti‐HSP60 IgG‐treated mice (13/13), with no reperfusion being observed. In contrast, 64% (9/14) of control mice had complete occlusion, with reperfusion occurring in 6/9 mice. Thrombi were significantly larger in anti‐HSP60 IgG‐treated mice (P = 0.0001), and contained four‐fold more inflammatory cells (P = 0.0281) than in controls. Non‐injured contralateral arteries of anti‐HSP60 IgG‐treated mice were also affected, exhibiting abnormal endothelial cell morphology and significantly greater von Willebrand factor (VWF) and P‐selectin expression than control mice (P = 0.0024 and P = 0.001, respectively). Conclusions: In summary, the presence of circulating anti‐HSP60 autoantibodies resulted in increased P‐selectin and VWF expression and altered cell morphology in endothelial cells lining uninjured carotid arteries, and promoted thrombosis and inflammatory cell recruitment in FeCl₃‐injured carotid arteries. These findings suggest that anti‐HSP60 autoantibodies may constitute an important prothrombotic risk factor in cardiovascular disease in human vascular disease.