Late perforation of the aortic root by an atrial septal defect occlusion device.
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Biomedical subjects
Publications and source records attributed to Martin Grapow.
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PURPOSE: Cryopreserved human blood vessels may become important tools in bypass surgery. Optimal cryopreservation of an arterial graft should, therefore, preserve both histological and physiological characteristics of smooth muscle and endothelium comparable to the unfrozen artery. METHODS: Rings from human internal mammary arteries (IMA) were investigated in vitro either unfrozen or after immersion into a cryomedium (RPMI 1640 containing 1.8M Me2SO and 0.1M sucrose) and cryostorage with and without surrounding medium. RESULTS: In unfrozen IMA, neither contractile responses to noradrenaline (NA) nor endothelium-dependent relaxant responses to acetylcholine (ACH) was modified after exposure of the IMA to cryomedium or during activation of protein kinase C by phorbol-12,13-dibutyrate (PDBu). Exposure to cryomedium with gradually increasing Me2SO content before starting the cooling process did not improve the post-thaw functional activity of the artery. Optimal post-thaw recovery of contractile responses to NA and PGF(2alpha) was observed after freezing at a speed of -1.2 and -3 degrees C/min in arteries stored with and without surrounding cryomedium. Compared to unfrozen controls, the ACH-induced endothelium-dependent relaxation during active tone induced by 3 microM PGF(2alpha) reached 16 and 56% after freezing with and without surrounding medium. All functional data were reflected by electron microscopy images showing considerably better preservation of the endothelial layer after freezing without medium. CONCLUSION: Freezing of human arteries at a mean cooling rate of -3 degrees C/min and storage without surrounding medium offers the prospect of optimal preservation of both smooth muscle and endothelial function in cryopreserved human IMA.
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Reactive oxygen species (ROS) are thought to be important mediators in ischaemia/reperfusion injury following coronary vasospasm. The most ubiquitous action of melatonin is that of a free radical scavenger. Therefore, we investigated the action of melatonin by monitoring changes in the tone on ring preparations from human internal mammary arteries (IMA). In quiescent IMA rings melatonin (0.1 nm-10 microm) never elicited any change in baseline tension but 1-100 nm melatonin enhanced significantly maximal responses to noradrenaline (NA) in arteries with endothelial function. In NA (1 microm) precontracted arteries inhibition of nitric oxide (NO(*)) formation by N(G)-monomethyl-L-arginine (l-NMMA, 100 and 400 microm) eliminated 43 +/- 7 and 61 +/- 7% of the acetylcholine (ACH) effect. Melatonin (100 and 400 nm) attenuated maximal endothelium-dependent relaxant responses to ACH slightly by 23 +/- 9 and 17 +/- 9% leaving responses to direct stimulation of soluble guanylate cyclase by sodium nitroprusside unchanged. Incubation of IMA for 20 hr at 37 degrees C with 1 microg/mL lipopolysaccharide (LPS) enhanced maximal NA effects to 147 +/- 18% (n = 22, P < 0.01) whereas 50 microg/mL LPS reduced the NA maxima to 68 +/- 9% (n = 10, P < 0.01) of the control effects. The LPS-induced potentiation was completely attenuated by coincubation with melatonin (400 nm) and significantly reduced by coincubation with the thromboxane synthase inhibitor dazoxiben (10 microm). It is suggested that the LPS-induced hyperreactivity of vascular smooth muscle is mediated through enhanced release of ROS and prostanoids and that melatonin inhibits the vascular hyperreactivity through selective scavenging of ROS.
Cardiovascular research of the past decades dealt with classical pathophysiological descriptions, then shifted toward the identification of relevant receptors, and then proceeded to the analysis of signal transduction pathways. Most recently, hand in hand with the achievements of the human genome project, the research has gone down the road toward molecular biological "disease gene(s) mapping". The application of proteome research will attempt to close the gap between genomic (and genetic) analysis and the physiological research. The rich source of heart surgery specimens represents an excellent starting point in data acquisition of proteomic context. Furthermore, animal models of cardiovascular diseases and deficiencies are considered, and will be explored. Examples of results from feasibility studies are given, with the emphasis on quantitative evaluation of proteomic components, hoping to discover co-regulated sets of proteins that are involved in any particular disease state. Identification of new, not yet discovered proteins will be pursued, though the emphasis of this work will be on the definition of characteristic sets of expressed proteins, which in turn might be able to delimit the state of disease and prognosis of therapy outcome. Besides the systematic issues, this paper refers to a number of methodological questions, like the comparison of the proteins detected by staining procedures and proteins detected in models in which biosynthetic labeling is applicable.