Effects of caffeine on energy output of rabbit heart muscle

The effects of caffeine (1 mmol·1⁻¹) on mechanical and energetic parameters in the arterially perfused interventricular rabbit septa were examined at various frequencies of stimulation. Even though 1 mmol⁻¹ caffeine induced a negative inotropic effect only at stimulation rates higher than 0.33 Hz. relaxation was impaired at all frequencies tested. The ratio between maximum rate of relaxation and developed tension $( - \dot T_{max} /T)$ was consistently lowered by caffeine, indicating a more marked effect on relaxation over contraction. In addition, while time-to-peak tension was unaffected by caffeine at the dose used, the last part of the relaxation (i.e., of the contractile event) was prolonged at all frequencies in the presence of the drug. Resting heat production (H _t ) was increased in the presence of caffeine (1.6±0.6 mW·g⁻¹). The ratios between active heat production and either developed tension (H_a/T) or tension time integral (H_a/TtI), increased at all frequencies examined (53.3±8.5 μJ·mN⁻¹·g⁻¹ and 68.2±9.9 μJ·mN⁻¹·s⁻¹·g⁻¹, respectively), indicating a lowered economy of the contractile process. This is consistent with the lower ATP/Ca ratio reported for the sarcoreticular Ca pump (i.e., one ATP hydrolyzed/2 Ca transported) with respect to the sarcolemmal mechanisms such as Na−Ca exchanger or the sarcolemmal Ca pump, with an ATP/Ca ratio of 1 to 1. Thus, inhibition of the SR-Ca pump by caffeine would induce a higher rate of ATP hydrolysis with the consequent increase in the H_a/T ratio. As a result of the increase in both H_a/T ratio and H_r induced by caffeine, the ratio between total heat production and developed tension (H_t/T) also increased. Therefore, the contractile process appeared to be more efficient in the presence of an active SR, since it is energetically less costly to generate a given level of isometric tension.