Heart rate changes caused by varying the oxygen supply to isolated hind legs of rats

Summary

In a rat with an isolated hind leg circulation perfused with varying tyrode solutions, heart rate (HR) changes were studied in dependence of$\dot V_{O_{_2 } }$ in the isolated hind leg and of$P_{CO_2 }$, [K⁺], pH and lactic acid concentration ([Lac]) measured in the venous outflow of the isolated hind leg. In experimental series I the inflow$P_{O_2 }$ $(P_{iO_2 } )$ was kept constantly high (either about 65 or 72 kPa). The perfusion pressure alternated between 16 and 24 kPa leading to flow rates in isolated hind legs ($\dot Q_a$) from 30 to 50 ml · 100 g⁻¹ · min⁻¹. The$\dot V_{O_{_2 } }$ depended on the momentary$\dot Q_a$ (flow-limited oxygen uptake). The [K⁺] and [Lac], the pH and the$AVD_{O_2 }$ remained nearly constant while the$P_{CO_2 }$ was lower at small flow rates. The HR decreases some 4 min after initial enhancement of$\dot Q_a$ and$\dot V_{O_{_2 } }$. Series II comprised experiments with low flow rates and a medium oxygen supply ($\dot Q_a$=2.5−17.4 ml · 100 g⁻¹ · min⁻¹),$P_{iO_2 }$=17.5−62.7 kPa). The$\dot V_{O_{_2 } }$ ranged between 0.02 and 0.2 ml · 100 g⁻¹ · min⁻¹. The [K⁺] and [Lac], the$P_{CO_2 }$ and the HR increased while the pH decreased. The [Lac] in the outflow showed a strong dependence on oxygen uptake and — at a weak oxygen supply — on the time. Cross-correlation analyses between the parameters confirmed that the HR was best temporally correlated to the [Lac] in the outflow. In series III a 17 min perfusion of normoxic solution ($P_{iO_2 }$=65.3 kPa) was followed by perfusion with a hypoxic tyrode solution ($P_{iO_2 }$=8.7 kPa).$\dot Q_a$ was 30 ml · 100 g⁻¹ · min⁻¹. The [Lac], the$P_{CO_2 }$ and the HR increased accompanied by a decrease in pH. However a HR increase was observed only when the actual values of [Lac],$P_{CO_2 }$ and pH exceeded their normal ranges for a resting muscle. The results support the hypothesis that heart rate is additionally influenced by metabolic muscle receptors measuring lactic acid concentration in working muscle.