Т1 mapping of rat lungs in 19 F MRI using octafluorocyclobutane.

PURPOSE: To demonstrate the feasibility of using octafluorocyclobutane (OFCB, c-C4 F8 ) for T1 mapping of lungs in 19 F MRI. METHODS: The study was performed at 7 T in three healthy rats and three rats with pulmonary hypertension. To increase the sensitivity of 19 F MRI, a bent-shaped RF coil with periodic metal strips structure was used. The double flip angle method was used to calculate normalized transmitting RF field (B1n + ) maps and for correcting T1 maps built with the variable flip angle (VFA) method. The ultrashort TE pulse sequence was applied for acquiring MR images throughout the study. RESULTS: The dependencies of OFCB relaxation times on its partial pressure in mixtures with oxygen, air, helium, and argon were obtained. T1 of OFCB linearly depended on its partial pressure with the slope of about 0.35 ms/kPa in the case of free diffusion. RF field inhomogeneity leads to distortion of T1 maps built with the VFA method, and therefore to high standard deviation of T1 in these maps. To improve the accuracy of the T1 maps, the B1n + maps were applied for VFA correction. This contributed to a 2-3-fold decrease in the SD of T1 values in the corresponding maps compared with T1 maps calculated without the correction. Three-dimensional T1 maps were obtained, and the mean T1 in healthy rat lungs was 35 ± 10 ms, and in rat lungs with pulmonary hypertension - 41 ± 9 ms. CONCLUSION: OFCB has a spin-rotational relaxation mechanism and can be used for 19 F T1 mapping of lungs. The calculated OFCB maps captured ventilation defects induced by edema.

Endothelin-converting enzyme inhibition in the rat model of acute heart failure: heart function and neurohormonal activation.

Endothelin-1 (ET-1) has been implicated in many cardiovascular diseases, including acute heart failure (AHF) due to myocardial ischemia. Previously we described the oral endothelin-converting enzyme (ECE) inhibitor, PP36, and in this study, we investigated its cardioprotective effect in more detail, and examined the role of PP36 in the neurohormonal activation in rats that had been subjected to acute myocardial ischemia due to the microsphere embolization of coronary microcirculation. PP36 treatment (3.5 x 10(-5) M/kg/day) led to a significant fourfold decrease in hypertensive response when big-ET-1 was administered to healthy, conscious rats. ECE inhibition did not affect mortality during the first 48 hours after ischemia initiation. Systemic hemodynamic, heart function, and neurohormonal activation were analyzed in the healthy control group, the AHF group, and the AHF+PP36 group two days after AHF induction. In conscious rats in the AHF+PP36 group, mean arterial pressure (MAP) was restored and became similar to that of the MAP of the control group. In anesthetized rats, in the AHF+PP36 group, MAP was not restored and was 22% lower than the MAP of the control group. Myocardial contractility was partially restored and cardiac relaxation significantly improved after PP36 application. Further analysis of cardiac output and peripheral resistance in anesthetized rats revealed no differences between the AHF group and the AHF+PP36 group. There were no differences in plasma ET-1 concentration, serum angiotensin converting enzyme activity, and in the adrenal glands' catecholamine content between the AHF group and the AHF+PP36 group. However, rats in the AHF+PP36 group demonstrated a 60% decrease in cardiac endothelial nitric oxide synthase (eNOS) protein expression, and a 56% reduction of myocardial norepinephrine release, when compared with the AHF group's animals. These results suggest that PP36 can preserve heart function during the recovery from acute ischemic injury, and may modulate the cardiac norepinephrine release and eNOS protein level.