| Objective To investigate the role of gap junctions and observe the therapeutic efficacy of their blocker, heptanol , in cerebral vasospasm (in vitro and in vivo). Method 1. In vitro: the effect of heptanol, a blocker of gap junctions, on the OxyHb-induced or K+-induced contraction of isolated rabbit basilar arteries were observed by an isometric tension-record method. 2. In vivo: the rabbit two-hemorrhage model was established by injection of autogenous blood into the cisterna magna and diameters of the basilar arteries were determined through arteriography. The therapeutic efficacy of heptanol was observed after given intraarterially and intracisternally. Light microscope was performed to assess the morphologic changes of the arteries examined. Result 1. In vitro: 10-4 mol/L OxyHb caused constant contractions lasting over 30 minutes in basilar arterial rings . 60 mmol/L K+ caused stronger and faster contractions than those induced by OxyHb. 10-4(10-2 mol/L heptanol significantly inhibited the contraction of basilar arterial rings induced both by 10-4 mol/L OxyHb and 60 mmol/L K+. The magnitude of the heptanol-induced relaxation was dose-dependent. With 500 μmol/L heptanol, the magnitude of the OxyHb-induced vasocontraction was reduced to sixty percent. While with 1 mmol/L heptanol, it was almost completelyinhibited. The inhibitory effect of heptanol on the K+-induced vasocontraction was also observed but it was not so strong as that on the OxyHb-induced. After pretreated arterial rings for ten minutes, heptanol (≥ 3×10-4 mol/L ) significantly decreased their responses to the OxyHb-induced contraction(P<0.01).With the concentration of 3×10-4 mol/L heptanol, the time course of OxyHb-induced contraction was unaltered , although the absolute magnitude of the response was decreased by nearly 40%. But with the same concentration of heptanol, the K+-induced contraction was not blocked. 2. In vivo: Basilar arterial vasospasm was appeared as early as 30 minutes (acute phase) after the first injection of the autogenous blood(0.5 ml/kg) into the cisterna magna and became more obvious as later as day 7 (chronic phase) after the second injections of blood on day 2. In the acute phase, basilar arterial vasospasm was released 10 minutes after intraarterial infusion of 0.2 mmol/kg heptanol. In the chronic phase, the diameters of the arteries did not significant changed on day 7 as compared to those of the arteries in control groups after the second injectons of blood and heptanol respectively on day 2. The results showed the therapeutic efficacy of heptanol in the acute and chronic cerebral vasospasm. When heptanol(0.02 mmol/kg) was previously injected intracistrnally 10 minutes before the first blood injection , the cerebral vasospasm was not obvious in the acute phase . And the vasospasm was also notpresented on day 7 after the second injections of heptanol and blood respectively on day 2. The results showed that heptanol could pre-inhibit the acute and chronic cerebral vasospasm .At autopsy, clotted blood was observed over the subarachnoid space and completely covered the basilar arteries. Through light microscope, the basilar arteries from day 7 rabbits of the control group had abnormalities including condensation of chromatin in endothelial cells, corrugation of internal elastic lamina, sparse distributing of smooth muscle cells, etc. The vessels of the intraarterial and intracisternal treatment group demonstrated less extensive degenerative changes. Conclusion 1. OxyHb is the principal spasmogen . 2. The rabbit two-hemorrhage model can mimic the clinical acute and chronic cerebral vasospasm. 3. Heptanol significantly inhibits the OxyHb-induced contraction of rabbit basilar arteries rings by selective disruption of gap junctions . 4. Heptanol can reverse or inhibit the acute and chronic cerebral vasospasm by given intraarterially or intracisternally. 5. The gap junctions may play a pathophysiological role in the cerebral vasospasm. Block of gap junctions is probably a new method for cer... |
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