Compensatory Hypertrophy Secondary To Pressure And Volume Overload Improves Myocardial Hypoperfusion/reperfusion Tolerance

Abstract

Concentric hypertrophy reduces hypoperfusion/reperfusion (H/R) tolerance of the myocardium. PURPOSE To examine whether exercise training, superimposed on concentric hypertrophy secondary to hypertension, could increase myocardial H/R tolerance. METHODS Female Wistar-Kyoto (W) and spontaneously hypertensive rats (SHR) (age:16 wks; N=40), were placed into a sedentary (S) or exercise training (T) group (treadmill running; 20 m/min, 1 hr/d, 5 d/wk for 16 wks). Four groups were studied: (W-S, n=10), (W-T, n=10), (SHR-S, n=10), (SHR-T, n=10). In situ blood pressure and heart rate were determined and in vitro isolated heart performance was measured with a retrogradely perfused, Langendorff, isovolumic preparation (16 ml/min, 5 Hz, 2 mM Ca2+, LVEDP set at 10 mmHg, 95% O2, 5% CO2). The H/R protocol consisted of a 75% reduction in coronary flow for 17 min followed by 30 min of reperfusion. RESULTS Although the rate-pressure product (RPP) was significantly elevated in SHR, bradycardia with T reduced the RPP in both W and SHR (W-S; 68873 ± 3152, W-T; 62372 ± 4582, SHR-S; 92755 ± 4464, SHR-T; 80271 ± 3450; p<0.05) without an attenuation in systolic blood pressure (W-S; 161 ± 7 mmHg, W-T;159 ± 6 mmHg, SHR-S; 187 ± 5 mmHg, SHR-T;181 ± 5 mmHg). Heart/body weight ratio was greater in SHR vs. W (p<0.001) (W-S; 4.2 ± 0.3 mg/g, W-T; 4.2 ± 0.2 mg/g, SHR-S; 4.9 ± 0.4 mg/g, SHR-T; 5.2 ± 0.2 mg/g). Interestingly, H/R tolerance was improved in SHR relative to W-S, by lowering diastolic pressure. At 30 minutes of reperfusion, the LVDevP in W-S was approximately 50% of SHR (W-S; 52.08 ± 20.3 mmHg, W-T; 107.9 ± 18.1 mmHg, SHR-S 125.15 ± 26.9 mmHg, SHR-T 99.5 ± 19.0 mmHg, p<0.05). This diminution of systolic pump function at 30 minutes of reperfusion in W-S was accompanied by an increased LVEDP (WS; 83.05 ± 18.9 mmHg, W-T; 41.4 ± 14.9, SHR-S; 32.5 ± 20.9 mmHg, SHR-T; 37.6 ± 16.4 mmHg). When normalized to GAPDH, HSP70 abundance was enhanced in W-T, SHR-S and SHR-T relative to W-S (W-S; 0.65 ± 0.085, W-T; 1.14 ± 0.13, SHR-S; 1.32 ± 0.01, SHR-T; 1.72 ± 0.12, p<0.05). CONCLUSION Both T and short-term hypertension result in a myocardium that is more tolerant to H/R injury, with no further putative protection gained by superimposing T on hypertension. Enhanced HSP70 abundance with compensatory hypertrophy may be involved in the improved tolerance observed. This study was supported by the Mid-Atlantic AHA: JRL