Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ
injury during clinical stetting for example for cardiopulmonary bypasses. The
generation of reactive oxygen species (ROS) during I/R induces oxidative stress
that promotes endothelial dysfunction, DNA dissociation and local inflammation.
In turn, those processes induce cytokine release, resulting in damage to cellular
structures and cell death. One of the major psychoactive compounds of
Cannabis is delta-9-tetrahydrocannabinol (-THC), which
is known as an anti-inflammatory mediator. Our research aimed to test if
-THC may be protective in the treatment of cardiovascular system
dysfunction arising from I/R heart injury. Methods: Two
experimental models were used: isolated rat hearts perfused with the Langendorff
method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent
ex vivo/chemical in vitro I/R protocol with/without
-THC treatment. The following parameters were measured: cell
metabolic activity, morphology changes, cell damage as lactate dehydrogenase
(LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant
capacity (TAC) and heart hemodynamic parameters. Results: -THC protected the heart, as evidenced by the improved recovery
of cardiac function (p 0.05, N = 3–6). Cells subjected to I/R
showed lower cytoplasmic LDH activity, and 10 M
-THC treatment reduced cell injury and increased LDH content
(p = 0.019, N = 6–9). Morphology changes of HCM-spherical shape,
vacuolisation of cytoplasm and swollen mitochondria—were inhibited due to
-THC treatment. I/R condition affected cell viability, but 10
M -THC decreased the number of dead cells
(p = 0.005, N = 6–9). The total level of CERK was lower in the I/R
group, reflecting oxidative/nitrosative stress changes. The administration of
-THC effectively increased the production of CERK to the level of
aerobic control (p = 0.028, N = 6–9). ROS level was significantly
decreased in I/R cells (p = 0.007, N = 6–8), confirming oxidative
stress, while administration of 10 M -THC enhanced
TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6–8).
Conclusions: -THC promotes the viability of
cardiomyocytes, improves their metabolic activity, decreases cell damage and
restores heart mechanical function, serving as a cardioprotective. We proposed
the use of -THC as a cardioprotective drug to be, administered
before onset of I/R protocol.