Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure

The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 ± 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 ± 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p < 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p < 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p < 0.01), and LV systolic wall stress increased (p < 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p < 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 ± 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 ± 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, especially related to subendocardial hypoperfusion.