A Selective TRPC3 Inhibitor Pyr3 Attenuates Myocardial Ischemia/Reperfusion Injury in Mice.

An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery. Our previous study has identified transient receptor potential channel 3 (TRPC3) and TRPC6 as cation channels through which most of the damaging calcium enters, aggravates pathological changes in vivo and increases ischemia/reperfusion (I/R) injury in mice. This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice. C57BL/6J wild-type male mice (8 to 12 weeks old) were anesthetized with 3.3% chloral hydrate. A murine I (30 min)/R (24 h) injury model was established by temporary occlusion of the left anterior descending (LAD) coronary artery. Pyr3 was administered at concentrations of 0, 2.5, 5, or 10 mg/kg via the right jugular vein 5 min before reperfusion. We observed that the selective TRPC3 inhibitor, 10 mg/kg Pyr3, significantly decreased the infarct size of left ventricle, and reduced the myocardial cell apoptosis rate and inflammatory response in mice. In a conclusion, TRPC3 can function as a candidate target for I/R injury prevention, and Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.

Effect of sex on biomechanical properties of the proper hepatic artery in pigs and humans for liver xenotransplant.

OBJECTIVES: This study investigated the relation between biomechanical properties of the proper hepatic artery and sex in pigs and humans to provide the theoretical basis for selecting suitable donor in pig-to-human liver xenotransplant. MATERIALS AND METHODS: The proper hepatic arteries of 32 Chinese Hubei white pigs (8 males, 8 females, 8 castrated males, and 8 ovariectomized females) and 10 deceased donors (5 human men, 5 human women) were obtained. The pressure-diameter relations of the proper hepatic arteries were measured on biomechanical test equipment to calculate the incremental elastic modulus (Einc), pressure-strain elastic modulus (Ep), volume elastic modulus (Ev), and compliance. Each sample was sliced into 5-µm frozen sections and stained with hematoxylin-eosin. RESULTS: There were significant differences in Einc (F=10.24; P = .001), Ep (F=3.75; P = .001), and Ev (F=3.41; P = .002) of the proper hepatic arteries of female, male, and gonadectomized pigs; females had the lowest elastic modulus and the gonadectomized group had the highest (P < .01). There was a significant difference in compliance of the porcine proper hepatic arteries between the sexes, highest in the female group and lowest in the gonadectomized group (P < .01). No difference in the elastic modulus and compliance of the proper hepatic artery between the male pig and the human man. There was no difference between the female pig and the human woman. CONCLUSIONS: There were differences in the biomechanical properties of the proper hepatic arteries of the female, male, and gonadectomized pigs. The biomechanical properties of the human men/women proper hepatic artery match those of the porcine male/female hepatic artery. The correlation between sex and biomechanical properties of the proper hepatic artery in pigs could imply that a pig of the same sex should be chosen for pig-to-human liver xenotransplant.

Morphological and biomechanical remodeling of the hepatic portal vein in a swine model of portal hypertension.

OBJECTIVES: To obtain the morphological and biomechanical remodeling of portal veins in swine with portal hypertension (PHT), so as to provide some mechanical references and theoretical basis for clinical practice about PHT. METHODS: Twenty white pigs were used in this study, 14 of them were subjected to both carbon tetrachloride- and pentobarbital-containing diet to induce experimental liver cirrhosis and PHT, and the remaining animals served as the normal controls. The morphological remodeling of portal veins was observed. Endothelial nitric oxide synthase expression profile in the vessel wall was assessed at both mRNA and protein level. The biomechanical changes of the hepatic portal veins were evaluated through assessing the following indicators: the incremental elastic modulus, pressure-strain elastic modulus, volume elastic modulus, and the incremental compliance. RESULTS: The swine PHT model was successfully established. The percentages for the microstructural components and the histological data significantly changed in the experimental group. Endothelial nitric oxide synthase expression was significantly downregulated in the portal veins of the experimental group. Three incremental elastic moduli (the incremental elastic modulus, pressure-strain elastic modulus, and volume elastic modulus) of the portal veins from PHT animals were significantly larger than those of the controls (P < 0.05), whereas the incremental compliance of hepatic portal vein decreased. CONCLUSIONS: Our study suggests that the morphological and biomechanical properties of swine hepatic portal veins change significantly during the PHT process, which may play a critical role in the development of PHT and serve as potential therapeutic targets during clinical practice.

Morphological and biomechanical remodelling of the hepatic artery in a swine model of portal hypertension.

OBJECTIVES: To obtain the biomechanical and morphological remodelling of hepatic arteries in swine with portal hypertension. METHODS: A number of 20 white pigs was used, of which 14 were subjected to liver cirrhosis and portal hypertension (PHT) induced by carbon tetrachloride and pentobarbital; the rest were used as the control group. The biomechanical remodelling of the hepatic arteries was measured, namely, the incremental elastic modulus (E inc), pressure-strain elastic modulus (E p), volume elastic modulus (E v), the incremental compliance (C), the opening angle and the stained microstructural components of the vessels. RESULTS: The percentages for the microstructural components and the histologic data significantly changed in the experimental group, three incremental elastic moduli (E inc, E p, and E v) of the experimental group were significantly larger than those of the control group (P < 0.05); the compliance of hepatic arteries decreased greatly (P < 0.05) too. The opening angle (OA) was considerably larger than that of control group (P < 0.05). CONCLUSIONS: The study suggests that the morphological and biomechanical properties of swine hepatic arteries have changed significantly during the process of portal hypertension and that from biomechanical aspects, the hepatic arteries have also suffered from extensive remodelling, which in turn deteriorates the existing portal hypertension.