Nitric oxide-generating agents are used for treating hypertensive crisis, but existing agents are limited by toxicity and tolerance. Nitrosyl-cobinamide (NO-cobinamide), a novel direct NO donor, may overcome these limitations. In addition, there is a need for non-invasive tissue perfusion assessment techniques to optimize antihypertensive therapy.
The blood pressure lowering and tissue perfusion effects of NO-cobinamide were examined initially in five normotensive rabbits at escalating doses. The anti-hypertensive response to NO-cobinamide was then tested in five rabbits made artificially hypertensive with phenylephrine. During each phase of the experiment, diffuse optical spectroscopy (using a prototype device we constructed) and continuous wave near infrared spectroscopy were used to non-invasively monitor oxygenation in peripheral tissues and brain region.
In normotensive rabbits, NO-cobinamide decreased blood pressure in a dose-related manner beginning at infusion rates of 8.6αg/kg/min. At similar infusion rates, NO-cobinamide decreased blood pressure in phenylephrine-induced hypertensive rabbits. Diffuse optical spectroscopy demonstrated increased deoxyhemoglobin and decreased oxyhemoglobin concentrations at high phenylephrine doses, with NO-cobinamide reversing these trends as blood pressure was lowered.
NO-cobinamide effectively lowered blood pressure in both normotensive and artificially-hypertensive rabbits, with more profound effects noted at higher doses. Diffuse optical spectroscopy successfully monitored tissue oxygenation during dynamic changes in systemic blood pressure.
NO-cobinamide, a direct NO donor, shows potential to be an effective alternative to other nitric oxide-generating agents that are limited by tolerance and adverse effects. Diffuse optical spectroscopy may be used to accurately monitor tissue perfusion and guide therapy with minimal invasiveness.
Steven Wong, No Financial Disclosure Information; No Product/Research Disclosure Information