OXYGEN COST OF STRESS DEVELOPMENT IN HYPERTROPHIED AND FAILING HEARTS FROM THE SPONTANEOUSLY HYPERTENSIVE RAT

Left ventricular isovolumic stress development and metabolic parameters were studied in 18-24-month-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rat controls using the isolated, isovolumic (balloon in left ventricle) buffer-perfused rat heart preparation. After WKY rats and all SHRs were compared, SHRs were divided into two groups: those animals with (SHR-F) and without (SHR-NF) evidence of heart failure. Hearts were perfused at 100 mm Hg using a constant pressure system at a temperature of 37-degrees-C. In the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak midwall stress was greatest in the WKY group and, again, lowest in the SHR-F group. Oxygen consumption was lowest in the SHR-F group. When the oxygen cost of stress development was estimated by normalizing myocardial oxygen consumption by peak developed midwall stress, values were lowest in the WKY, greater in the SHR-NF, and greatest in the SHR-F group. Lactate production did not occur in the baseline state in any of the groups. Functional and metabolic responses to graded hypoxia, induced by changing the gas mixture of the perfusate from 95% to 50%, 25%, and 0% oxygen at perfusion pressures of 100 and 130 mm Hg, were studied. Increasing perfusion pressure generally resulted in small increases in peak systolic pressure and myocardial oxygen consumption but did not substantially reverse the contractile or metabolic deficit present in the SHR-F group. Graded hypoxia resulted in declines in peak midwall stress and myocardial oxygen consumption, and increases in lactate production in all groups; the oxygen cost of stress development continued to be greatest in the SHR-F group. Thus, peak systolic stress development is progressively impaired during the transition from hypertrophy to failure in the SHR. Although the oxygen cost of stress development appears to be increased in hypertrophied and to a greater degree in failing myocardium, the present isolated heart data provide no evidence to suggest that the baseline depression of isovolumic stress development in the SHR-F is due to hypoxia.