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Effects of mannitol on cardiac ultrastructure and microcirculation following anoxia
Abstract:
Electron microscopic and microcirculatory effects of hyperosmolal mannitol were evaluated in the isolated perfused isovolumic rat heart. Specimens for ultrastructural examination were obtained in 26 experiemnts after 15 min of sequential aerobic, anoxic, and reoxygenated perfusion using an isosmolal perfusate of Krebs-Ringer-Henseleit bicarbonate buffer (KRB) (osmolality equals 290 mosmol/kg) vs. a hyperosmolal solution of KRB + mannitol (equals 350 mosmol/kg). No significant changes were noted during aerobic perfusion. Anoxic hearts perfused with isosmolal KRB demonstrated the most severe ultrastructural alterations including: mitochondrial swelling with disruption of cristae, myofibrillar fusion and contraction bands, and subsarcolemmal edema and vacuolization. These subcellular changes were not only partially reversed by oxygenated isosmolal perfusion but were significantly reversed during both the anoxic and reoxygenation perfusion periods with mannitol added. Following silicone rubber injection of the microcirculation, only focal capillary endothelial cell swelling was noted, and no difference in arteriolar or capillary filling was observed with either perfusate. Thus, mannitol significantly reversed the postanoxic ultrastructural changes consistently observed in the absence of increased osmolality. No gross effect on vascular patency could be demonstrated.
Insights
Hyperosmolal mannitol significantly reversed postanoxic ultrastructural damage in isolated rat hearts. Mannitol mitigated cellular damage during anoxia and reoxygenation without affecting microcirculation patency.
Area of Science:
- Cardiology
- Cell Biology
- Physiology
Background:
- Ischemia-reperfusion injury significantly impacts heart function.
- Understanding cellular mechanisms of injury and protection is crucial.
- Hyperosmolar agents are explored for cardioprotective effects.
Purpose of the Study:
- To evaluate the electron microscopic and microcirculatory effects of hyperosmolar mannitol in an isolated perfused rat heart model.
- To determine if hyperosmolar mannitol can mitigate anoxic and reoxygenation-induced ultrastructural damage.
Main Methods:
- Isolated isovolumic rat hearts were perfused sequentially with aerobic, anoxic, and reoxygenated Krebs-Ringer-Henseleit bicarbonate buffer (KRB).
- Perfusates were either isosmolal (290 mOsm/kg) or hyperosmolar (350 mOsm/kg) with mannitol.
- Ultrastructural changes were examined using electron microscopy; microcirculation was assessed via silicone rubber injection.
Main Results:
- Anoxic perfusion with isosmolal KRB caused severe ultrastructural damage, including mitochondrial swelling and myofibrillar changes.
- Hyperosmolar mannitol significantly reversed these postanoxic changes during both anoxic and reoxygenation periods.
- No significant differences in arteriolar or capillary filling were observed, with only focal capillary endothelial cell swelling noted.
Conclusions:
- Hyperosmolar mannitol demonstrates significant cardioprotective effects by reversing postanoxic ultrastructural damage.
- Mannitol's protective mechanism appears to act at the cellular level, independent of microcirculatory patency changes.
- These findings suggest a potential therapeutic role for hyperosmolar mannitol in managing cardiac ischemia-reperfusion injury.