Submitted on September 16, 2003
Accepted on November 16, 2004
Reduced Oxygen Supply Explains the Negative Force-Frequency Relation and the Positive Inotropic Effect of Adenosine in Buffer Perfused Hearts
Rodrigo M Marin1 and Kleber G Franchini1*
1 Department of Internal Medicine, State University of Campinas, Campinas, SP, Brazil
* To whom correspondence should be addressed. E-mail: franchin{at}unicamp.br.
We, herein, examine, in isolated rat hearts perfused with Hepes and red blood cell-enriched buffer, the changes in the left ventricular pressure induced by increases in heart rate or infusion of adenosine in order to investigate whether the negative force-frequency relationship and the positive inotropic effect of adenosine are related to an inadequate oxygen supply provided by crystalloid perfusates. Hearts perfused with Hepes buffer at a constant flow demonstrated a negative force-frequency relationship, while a positive force-frequency relationship was observed in hearts perfused with red blood cell-enriched buffer. In contrast, Hepes perfused hearts showed a concentration-dependent increase in left ventricular systolic pressure (EC50 of 7.0±1.2 nM; Emax of 104 ± 2 mmHg at 0.1 µM; baseline 84 ± 2 mmHg) in response to adenosine, while no change was observed in the left ventricular pressure of the hearts perfused with buffer enriched with red blood cells. The positive inotropic effect of adenosine correlated with the simultaneous reduction in heart rate (r=0.67, p<0.01; EC50 of 3.8±1.4 nM, baseline 228 ± 21 to a minimum of 183 ± 22 beats/min at 0.1 µM) and it was abolished in isolated hearts paced to suppress the adenosine-induced bradycardia. In conclusion, these results indicate that both the negative force-frequency relationship and the positive inotropic effect of adenosine in isolated rat heart are related to myocardial hypoxia rather then to functional peculiarities of rat heart.
