Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.
We tested the hypothesis that isoproterenol would increase myocardial work and O2 consumption at reduced efficiency and that both left ventricular hypertrophy and chemical sympathectomy would lead to changes in this myocardial efficiency response. Left ventricular hypertrophy was produced by aortic valve plication in 23 puppies. Six months later, sympathetic denervation (6-hydroxydopamine) was produced in 12 hypertrophied and 10 non-hypertrophied dogs, 5 days prior to acute experiments. Ten non-hypertrophied and 11 hypertrophied animals were not denervated. Measurements were made before and during an isoproterenol infusion (0.5 microgram/kg/ min). Regional myocardial work was calculated as the integrated product of force (miniature transducer) and segment shortening (ultrasonic crystals). Regional O2 consumption was calculated from regional blood flow (microspheres) and regional O2 saturations (microspectrophotometry). In all groups, regional O2 consumption increased with isoproterenol (non-hypertrophied, non-sympathectomized 6.5 +/- 0.8 to 20.3 +/- 5 ml O2/min/100 g, non-hypertrophied, sympathectomized 5.0 +/- 0.7 to 10.0 +/- 1.5, hypertrophied, non-sympathectomized 9.8 +/- 1.3 to 16.2 +/- 2.2, hypertrophied, sympathectomized 6.1 +/- 0.5 to 13.3 +/- 1.6). Regional segment work also increased in all groups with isoproterenol stimulation (non-hypertrophied, non-sympathectomized 781 +/- 73 to 1197 +/- 61 g.mm/min, non-hypertrophied, sympathectomized 996 +/- 221 to 2118 +/- 412, hypertrophied, non-sympathectomized 1031 +/- 145 to 3262 +/- 753, hypertrophied, sympathectomized 721 +/- 116 to 1745 +/- 402). In the non-hypertrophied, non-sympathectomized group, efficiency (work/O2 consumption) was significantly decreased from 122 +/- 17 to 76 +/- 9 g.mm/ml O2/100 g demonstrating an "oxygen wasting" effect. In the hypertrophied, non-sympathectomized group, segment efficiency significantly increased from 94 +/- 19 to 250 +/- 63. In both sympathectomized groups, efficiency was not altered by isoproterenol. Thus the oxygen wasting effect of beta-adrenergic stimulation was reversed by left ventricular hypertrophy and blocked by sympathectomy.
In a dog model of left ventricular hypertrophy (LVH) created by aortic valve plication, we examined the hypothesis that regional myocardial inotropic and metabolic responses to alpha-adrenergic stimulation would be diminished due to decreased alpha-adrenoceptor number. After systemic beta-adrenergic blockade, phenylephrine (PE, 5 micrograms.kg-1.min-1) was infused into the left anterior descending artery in eight LVH and nine control open-chest anesthetized dogs. The circumflex region served as control. In both regions, local segment work was calculated as the integrated products of force (miniature transducer) and segment shortening (ultrasonic crystals). Local myocardial O2 consumption was calculated from regional blood flow (microspheres) and O2 saturation (microspectrophotometry). A saturation radioligand binding assay was used to determine adrenoceptor number and affinity. In control animals in the treated region, PE increased work from 815 +/- 140 to 1,493 +/- 149 g.mm.min-1. In LVH, work was not significantly altered (688 +/- 142 vs. 730 +/- 149 g.mm.min-1). Regional blood flow was elevated in controls (81 +/- 10 to 141 +/- 24 ml.min-1.100 g-1) but was not changed in LVH (105 +/- 12 vs. 123 +/- 18 ml.min-1.100 g-1). In controls, but not in LVH, myocardial O2 consumption was almost doubled during PE infusion (6.2 +/- 0.9 vs. 12.0 +/- 2.1 ml O2.min-1.100 g-1). alpha-Adrenoceptor number and dissociation constants values were not different between control and LVH (15.7 +/- 2.8 vs. 16.4 +/- 2.7 fmol/mg protein; 13.2 +/- 3.4 vs. 16.9 +/- 4.3 nm, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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