Effect of acute alpha adrenergic stimulation on cardiac function

Background. Phenylephrine (PE) is a α-adrenergic agent commonly administered by perfusion and anesthesia. It is important to identify the effect of PE, especially on cardiac function. This study was intended to show the effects of PE on cardiac function in the murine model via pressure-volume loops. Methods. Six C57BL/6J twelve-week-old female mice were studied prior to and following PE administration at 50 μg/kg IV. In vivo pressure-volume loops were recorded at both time points. Results. There was an expected increase in maximum arterial pressure by 30% (p < 0.001) and end-systolic pressure by 34% (p < 0.001). However, there was a decrease in cardiac output by 30% (p = 0.0006), ejection fraction by 36% (p = 0.0003) and stroke volume by 25% (p < 0.004). Conclusions. This study demonstrates that PE has an effect on cardiac function beyond increasing vascular resistance. The data suggest the negative effects of PE on cardiac function may be related to stimulation of cardiac α-adrenergic receptors. Perfusion (2007) 22, 289—292.

Effect of BDM, verapamil, and cardiac work on mitochondrial membrane potential in perfused rat hearts

The biochemical link providing effective coordination between the mitochondrial ATP synthetic machinery and the contractile apparatus following transitions in cardiac work remains enigmatic. Studies were designed to determine whether activation of the actomyosin adenosinetriphosphatase (ATPase) is a necessary part of the signaling mechanism to the mitochondrial ATP synthase or whether a rise in cytosolic free Ca2+ is sufficient to activate the synthase. With the use of Langendorff-perfused rat hearts, cardiac work was varied via changes in perfusion pressure and by the inclusion of a beta-adrenergic agent. Furthermore, 2,3-butanedione monoxime and verapamil were used to vary independently either the activity of the actomyosin ATPase or the level of cytosolic free Ca2+. Determinations of the in vivo mitochondrial membrane potential [delta psi m; see Wan et al. Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H445-H452, 1993] and its vectorial displacement during work transitions provide valuable information concerning direct activation of the ATP synthase and proton movement through the membrane domain of the synthase. Increased cardiac work in the presence of the beta-adrenergic agent resulted in a decrease in delta psi m. Addition of 2,3-butanedione monoxime decreased cardiac work but did not change delta psi m. The inclusion of verapamil resulted in similar decreases in cardiac work. However, delta psi m reversed back to a value observed under control, low-work conditions. These results in conjunction with data regarding levels of high-energy phosphates, free Mg2+, and adenosine 3',5'-cyclic monophosphate suggest a Ca(2+)-mediated increase in the activity of the ATP synthase.