Cryopreservation of human blood vessels may become an important tool in bypass surgery and peripheral vascular reconstruction. Ideally cryopreservation of a blood vessel should preserve functional characteristics comparable to those of fresh controls. The key advantage of cryopreservation is the fact that storage at deep subzero temperatures allows storage of structurally intact living vascular tissues for virtually infinite time. Originally developed for long-time storage of isolated cells, the techniques of cryopreservation of tissues are challenged by the fact that these are complex multicellular systems containing diverse types of cells with differing requirements for optimal preservation. Therefore, the post-thaw functional activity of vascular tissues is determined by the type of blood vessel and, in addition, by the cell packing effect. Moreover, evidence from pharmacological studies suggests that cryopreservation induces tissue specific changes in transmembrane signaling and the mechanisms coupling intracellular calcium release, sensitivity and calcium entry into the smooth muscle cells.

The affinities of 16 5-hydroxytryptamine (5-HT) receptor agonists (indole derivatives) and 7 5-HT receptor antagonists for [3H]5-hydroxytryptamine [( 3H]5-HT) binding sites in rat cerebral cortex membranes were determined. In addition, the potencies of the agonists for inhibiting the electrically induced tritium overflow from rat brain cortex slices preincubated with [3H]5-HT and from canine saphenous veins preincubated with [3H]noradrenaline were measured. Furthermore, the potencies of the indole derivatives for inducing contractile responses of canine saphenous veins were recorded. In addition, the interaction of the antagonists with unlabelled 5-HT at the 5-HT autoreceptor was studied in rat brain cortex slices. There was a good correlation between the binding affinities of the indole derivatives for the [3H]5-HT sites of rat brain cortex membranes and their potencies for inhibiting the evoked tritium overflow from both rat brain cortex slices and strips of canine saphenous vein. Comparison of the inhibition constants derived from the overflow experiments in both tissues again revealed a high correlation coefficient while there was only weak correlation between the binding affinities in rat brain cortex and the contractile potencies of the drugs in canine saphenous vein strips. When 5-HT receptor antagonists were investigated, metitepin and metergoline showed moderate affinities for the 5-HT autoreceptors in rat brain cortex slices, whereas quipazine had only weak affinity, and ketanserin, metoclopramide, cinanserin and cyproheptadine exhibited no antagonistic property. In binding experiments, the competition curves of most 5-HT receptor antagonists were biphasic, suggesting that the [3H]5-HT binding sites are heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS)

Dihydroergotamine (DHE) and 5 of its main metabolites, namely 8'-hydroxy-dihydroergotamine (8'-OH-DHE), 8',10'-dihydroxy-dihydroergotamine (8',10'-OH-DHE), 2,3seco,N(1)formyl,3-keto,8'-hydroxy-dihydroergotamine (8'-OH,N(1)formyl-DHE), dihydrolysergic acid amide (DH-LSA) and dihydrolysergic acid (DH-LS) were investigated on human and canine veins in vitro, on canine veins in situ, and in the ganglion-blocked rat in vivo. Like DHE, the metabolites 8'-OH-DHE, 8', 10'-OH-DHE and DH-LSA caused constriction of human varicose veins and only weak alpha-adrenoceptor blockade. On canine femoral vein strips the same compounds produced predominantly alpha-adrenoceptor blockade and only negligible stimulation. 8'-OH,N(1)formyl-DHE and DH-LS were largely inactive. The same compounds, which were agonists on human vein strips in vitro, induced dose-dependent reduction of venous compliance when infused locally into the dog saphenous vein in situ. In the ganglion-blocked rat, only 8'-OH-DHE and 8',10'-OH-DHE besides the parent drug produced an increase in diastolic blood pressure when injected intravenously. It is concluded that DHE metabolites with considerable venoconstrictor activity may contribute to the selective therapeutic action of DHE.

Cryopreservation of human IMA under the conditions applied in this study (1) attenuated endothelial cell function and (2) induced an activation of protein kinase C, thereby increasing calcium influx through dihydropyridine-sensitive calcium channels. These experimental data suggest that postoperative administration of calcium channel blockers alone or combined with long-acting nitrates should effectively prevent the development of spasms in arterial grafts.

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