Effect of temperature on glyceryl trinitrate induced relaxation of rabbit aorta

1993 ◽  
Vol 71 (8) ◽  
pp. 629-632 ◽  
Author(s):  
Brian P. Booth ◽  
James F. Brien ◽  
Gerald S. Marks ◽  
Kanji Nakatsu

It has previously been shown that the vasodilatory response to glyceryl trinitrate (GTN) was decreased during hypothermic cardiopulmonary bypass. The purpose of these experiments was to determine the effect of temperature on GTN-induced relaxation and on GTN biotransformation in rabbit aorta. It was determined that the EC50 of GTN on rabbit aortic rings (RARs) was increased significantly from 1.8 × 10−8 M at 37 °C to 3.4 × 10−8 M at 27 °C (p < 0.05). The production of NO by rabbit aortic strips (RASs) was significantly less at 27 °C compared with 37 °C after 80 min, being 9.62 × 10−11 ± 13.2 × 10−11 mol NO/g wet wt. RASs compared with 5.71 × 10−10 ± 9.43 × 10−11 mol NO/g wet wt. RASs, respectively (p < 0.05), after 80 min incubation. There was no difference in the amount of glyceryl-1,2-dinitrate (1,2-GDN) produced from GTN at the two temperatures. The ED20 for NO-induced relaxation of RARs increased from 3.46 × 10−10 ± 2.24 × 10−10 mol at 37 °C to 1.01 × 10−9 ± 4.51 × 10−10 mol at 27 °C (p < 0.05). These data indicate that the biotransformation of GTN and the release of NO were impaired by hypothermia, and that this, as well as a decrease in the tissue response to NO at 27 °C, explains the decrease in GTN activity at reduced body temperatures.Key words: glyceryl trinitrate, nitric oxide, temperature, rabbit aorta, vasodilation.

1998 ◽  
Vol 88 (6) ◽  
pp. 1614-1623 ◽  
Author(s):  
Bradley J. Hindman ◽  
Sakae Enomoto ◽  
Franklin Dexter ◽  
James N. Bates ◽  
Gilbert Aldape ◽  
...  

Background Cardiopulmonary bypass causes activation of leukocytes and increased concentrations of proinflammatory mediators, which may result in endothelial dysfunction. Because hypothermia attenuates many inflammatory processes, the authors hypothesized that hypothermic cardiopulmonary bypass would be associated with better endothelial function than normothermic cardiopulmonary bypass. Methods Isoflurane-anesthetized New Zealand White rabbits were randomized to undergo 90 min of either normothermic (37 degrees C, n=9) or hypothermic (27 degrees C, n=9) cardiopulmonary bypass with terminal rewarming. A third group served as anesthetized normothermic non-cardiopulmonary bypass surgical controls (n=8). Basilar artery and descending thoracic aorta were isolated from each animal. In vitro vessel relaxation responses to increasing concentrations of acetylcholine (which induces endothelial release of nitric oxide) and nitroprusside (which provides exogenous nitric oxide) were measured in phenylephrine-precontracted vessel rings. Results There were no differences in vessel relaxation responses between normothermic and hypothermic cardiopulmonary bypass groups in basilar artery or aorta. In contrast, basilar arteries from non-cardiopulmonary bypass controls had increased relaxation responses to both acetylcholine (P=0.004) and nitroprusside (P=0.031) compared with the pooled cardiopulmonary bypass animal data. Conclusions The authors observed no differences in endothelial or vascular smooth muscle function between normothermic and hypothermic cardiopulmonary bypass groups. Compared with non-cardiopulmonary bypass controls, cardiopulmonary bypass appeared to decrease basilar artery smooth muscle relaxation in response to endogenous and exogenous nitric oxide.


1988 ◽  
Vol 66 (10) ◽  
pp. 1344-1346 ◽  
Author(s):  
Christopher J. Slack ◽  
Brian E. McLaughlin ◽  
Kanji Nakatsu ◽  
Gerald S. Marks ◽  
James F. Brien

It is postulated that the organic nitrate vasodilator agents, including glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN), are prodrugs, such that biotransformation to the active inorganic metabolite, nitric oxide (NO), occurs prior to the onset of vasodilation. Furthermore, it is proposed that organic nitrate tolerance in vascular tissue involves decreased formation of NO. To test this latter hypothesis, we examined vasodilation induced by NO, GTN, and ISDN in non-tolerant, GTN-tolerant, and ISDN-tolerant rabbit aortic rings (RARs). Isolated RARs were contracted submaximally with phenylephrine; the time of onset of relaxation and percent relaxation of tissue were determined in response to NO (0.3 μM), GTN (0.03 μM), and ISDN (0.12 μM) before and after a 1-h treatment with 500 μM GTN, 500 μM ISDN, or buffer only. The data demonstrated that the response to NO was not changed in GTN-tolerant and ISDN-tolerant tissues, in which there was virtually no GTN-induced or ISDN-induced relaxation. These results are consistent with the postulate that organic nitrate vasodilator drugs must undergo biotransformation to NO before vasodilation can occur and that the mechanism of organic nitrate tolerance involves decreased formation of NO.


Author(s):  
Ivar Gøthgen ◽  
Ole Siggaard-Andersen ◽  
Jens Rasmussen ◽  
Peter Wimberley ◽  
Niels Fogh. Andersen

Circulation ◽  
1995 ◽  
Vol 92 (7) ◽  
pp. 1876-1882 ◽  
Author(s):  
Alexander Mülsch ◽  
Peter Mordvintcev ◽  
Eberhard Bassenge ◽  
Frank Jung ◽  
Bernd Clement ◽  
...  

Perfusion ◽  
2021 ◽  
pp. 026765912110148
Author(s):  
Joseph Mc Loughlin ◽  
Lorraine Browne ◽  
John Hinchion

Objectives: Cardiac surgery using cardiopulmonary bypass frequently provokes a systemic inflammatory response syndrome. This can lead to the development of low cardiac output syndrome (LCOS). Both of these can affect morbidity and mortality. This study is a systematic review of the impact of gaseous nitric oxide (gNO), delivered via the cardiopulmonary bypass (CPB) circuit during cardiac surgery, on post-operative outcomes. It aims to summarise the evidence available, to assess the effectiveness of gNO via the CPB circuit on outcomes, and highlight areas of further research needed to develop this hypothesis. Methods: A comprehensive search of Pubmed, Embase, Web of Science and the Cochrane Library was performed in May 2020. Only randomised control trials (RCTs) were considered. Results: Three studies were identified with a total of 274 patients. There was variation in the outcomes measures used across the studies. These studies demonstrate there is evidence that this intervention may contribute towards cardioprotection. Significant reductions in cardiac troponin I (cTnI) levels and lower vasoactive inotrope scores were seen in intervention groups. A high degree of heterogeneity between the studies exists. Meta-analysis of the duration of mechanical ventilation, length of ICU stay and length of hospital stay showed no significant differences. Conclusion: This systematic review explored the findings of three pilot RCTs. Overall the hypothesis that NO delivered via the CPB circuit can provide cardioprotection has been supported by this study. There remains a significant gap in the evidence, further high-quality research is required in both the adult and paediatric populations.


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