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Effects of low Ca++ reperfusion on rabbit heart mitochondrial function following autolysis
j Mol Cell Cardiol 19 (Supplement IV) (1987)
214
PYRUVATE CAN PRODUCE CONCENTRATION-DEPENDENT HEMODYNAMIC RECOVERY IN POSTISCHEMIC LACTAYEMIC WORKING GUINEA-PIG HEART. R. BUnger, R.T. Mallet, and D.A. Hartman. Department of Physiology, Uniformed Services University, Bethesda, MD 20814. Exogenously supplied pyruvate can accelerate hemodynamic and metabolic recovery following short-term (45 min) hypoxia and low-flow acidotic ischemia (JMCC 18:423-438, 1986; Fed Proe 45: 1040, 1986; Physiologist 29: 164, 1986). The beneficial effects of pyruvate on postisehemic heart rate-pressure product (HR x AP;IO -J cm H20/min ) and pressure-volume work (CO x AP; mJ/min x g wet wt) were concentratlon-dependent in hearts (preload: 13 em H20 ) utilizing 5 mM glucose (+5 U/L insulin) plus 5 mM lactate. [Pyr] Preischemia Postischemia % Recovery (mM) n HR x AP CO x AP HR x AP CO x AP HR x AP CO x AP 0 9 18.2 171 4.4 4.6 24.2 2.9 0.2 4 18.3 172 9.4* 13.6" 52.1" 7.7* 2.0 ii 19.1 204 12.4" 22.1" 65.8* 11.8" i0.0 6 19.9 205 18.9" 53.0*w 95.0*w 25.6*w *: P
2 1 5 THE DURATION OF AEROBIC METABOLISM DURING GLOBAL ISCHEMIA IS ONLY MODESTLY PROLONGED BY HYPOTHERMIA. L. W. V. DeBoer, R. R. Rabjohns, D. K. Swanson, University of Wisconsin, Madison, WI, U.S.A. After coronary blood flow ceases, anaerobic metabolism occurs. We determined the duration of aerobic conditions (i.e., the functional oxygen reserve) and the relationship of functional oxygen reserve to temperature. The epicardium of six buffer perfused rat hearts was illuminated with ultraviolet light and NADH fluorescence monitored "on-line" (NADH accumulation occurs at oxygen tensions under I TORR). We quantified the time to 50% fluorescence as T 1/2, latency as time to 10% fluorescence, and the rate of NADH appearance as a slope in percentage/min. TEMP T I/2 (see.) T latent (see) Slope (% fluor/min) 37 13.2 + 1.2 4.4 + 0.5 320 + 27 30 30.5 ~ 3.5 14.6 $ 2.3 193 T 22 20 54.3 T 7.7 32.8 ~ 6.0 139 ~ 15 13 81.9 ~ 7.7 49.8 $ 7.8 87 ~ 7 In previous experime-nts of oxygenated ~ardioplegia, the reTationship of T 1/2 to temperature was 4.8 sec/degree. In contrast, we found with normal K+ the relationship is 2.8 see/degree (r=.79). We conclude the functional oxygen reserve of the buffer perfused heart is small and is increased by hypothermia. Supported by a Grant-in-Aid from the American Heart Association
216
EFFECTS OF LOW Ca++ REPERFUSION ON RABBIT HEART MITOCHONDRIAL FUNCTION FOLLOWING AUTOLYSIS. T.R. Snow, T. Tapp. Cardiovascular Section, Oklahoma Medical Research Foundation; Oklahoma City, OK. Studies were performed on isolated rabbit heart mitoehondria (MITO) to determine whether reperfusion with low Ca q~" (L-Ca;0.1 mM) would decrease the loss of function accompanying varying periods of autolysis. Mitochondrial function was determined by the response to ADP (respiratory control index-RCl), and the rate of Ca ++ uptake. Increasing the period of the ischemic episode (IE) produced a montonic decrease in the RCI independent of the Ca++ in the reperfusate. For 2.5 mM Caq-P (H-Ca), the RCI decreased from 11.2• to 1.7• for 0.i mM Ca++, 12.5• to 2.3• A decrease in State 3 VO 2 was primarily responsible for this decrease; for longer periods, both State 3 and State 4 rates were depressed. The rates of Ca ++ uptake were also depressed by increasing the ischemic period. However, L-Ca perfusion was associated with a significantly smaller decrease 172• to 135• nm/mg/min as compared with H-Ca: 130• to 36• nm/mg/min. The amount of Ca++ which the MITO could sequester before spontaneous release was also affected by the duration of the IE and by the Ca++ in the reperfusate. Under control conditions, the MITO could readily retain i00 nm/mg protein. After 45 min IE, 50 nm/mg was the maximum Ca++ load before significant release occurred in MITO from L-Ca hearts and 25 nm/mg in the H-Ca hearts. These data suggest Ca++ overload is not responsible for MITO dysfunction accompanying an IE.
S.72
214
PYRUVATE CAN PRODUCE CONCENTRATION-DEPENDENT HEMODYNAMIC RECOVERY IN POSTISCHEMIC LACTAYEMIC WORKING GUINEA-PIG HEART. R. BUnger, R.T. Mallet, and D.A. Hartman. Department of Physiology, Uniformed Services University, Bethesda, MD 20814. Exogenously supplied pyruvate can accelerate hemodynamic and metabolic recovery following short-term (45 min) hypoxia and low-flow acidotic ischemia (JMCC 18:423-438, 1986; Fed Proe 45: 1040, 1986; Physiologist 29: 164, 1986). The beneficial effects of pyruvate on postisehemic heart rate-pressure product (HR x AP;IO -J cm H20/min ) and pressure-volume work (CO x AP; mJ/min x g wet wt) were concentratlon-dependent in hearts (preload: 13 em H20 ) utilizing 5 mM glucose (+5 U/L insulin) plus 5 mM lactate. [Pyr] Preischemia Postischemia % Recovery (mM) n HR x AP CO x AP HR x AP CO x AP HR x AP CO x AP 0 9 18.2 171 4.4 4.6 24.2 2.9 0.2 4 18.3 172 9.4* 13.6" 52.1" 7.7* 2.0 ii 19.1 204 12.4" 22.1" 65.8* 11.8" i0.0 6 19.9 205 18.9" 53.0*w 95.0*w 25.6*w *: P
2 1 5 THE DURATION OF AEROBIC METABOLISM DURING GLOBAL ISCHEMIA IS ONLY MODESTLY PROLONGED BY HYPOTHERMIA. L. W. V. DeBoer, R. R. Rabjohns, D. K. Swanson, University of Wisconsin, Madison, WI, U.S.A. After coronary blood flow ceases, anaerobic metabolism occurs. We determined the duration of aerobic conditions (i.e., the functional oxygen reserve) and the relationship of functional oxygen reserve to temperature. The epicardium of six buffer perfused rat hearts was illuminated with ultraviolet light and NADH fluorescence monitored "on-line" (NADH accumulation occurs at oxygen tensions under I TORR). We quantified the time to 50% fluorescence as T 1/2, latency as time to 10% fluorescence, and the rate of NADH appearance as a slope in percentage/min. TEMP T I/2 (see.) T latent (see) Slope (% fluor/min) 37 13.2 + 1.2 4.4 + 0.5 320 + 27 30 30.5 ~ 3.5 14.6 $ 2.3 193 T 22 20 54.3 T 7.7 32.8 ~ 6.0 139 ~ 15 13 81.9 ~ 7.7 49.8 $ 7.8 87 ~ 7 In previous experime-nts of oxygenated ~ardioplegia, the reTationship of T 1/2 to temperature was 4.8 sec/degree. In contrast, we found with normal K+ the relationship is 2.8 see/degree (r=.79). We conclude the functional oxygen reserve of the buffer perfused heart is small and is increased by hypothermia. Supported by a Grant-in-Aid from the American Heart Association
216
EFFECTS OF LOW Ca++ REPERFUSION ON RABBIT HEART MITOCHONDRIAL FUNCTION FOLLOWING AUTOLYSIS. T.R. Snow, T. Tapp. Cardiovascular Section, Oklahoma Medical Research Foundation; Oklahoma City, OK. Studies were performed on isolated rabbit heart mitoehondria (MITO) to determine whether reperfusion with low Ca q~" (L-Ca;0.1 mM) would decrease the loss of function accompanying varying periods of autolysis. Mitochondrial function was determined by the response to ADP (respiratory control index-RCl), and the rate of Ca ++ uptake. Increasing the period of the ischemic episode (IE) produced a montonic decrease in the RCI independent of the Ca++ in the reperfusate. For 2.5 mM Caq-P (H-Ca), the RCI decreased from 11.2• to 1.7• for 0.i mM Ca++, 12.5• to 2.3• A decrease in State 3 VO 2 was primarily responsible for this decrease; for longer periods, both State 3 and State 4 rates were depressed. The rates of Ca ++ uptake were also depressed by increasing the ischemic period. However, L-Ca perfusion was associated with a significantly smaller decrease 172• to 135• nm/mg/min as compared with H-Ca: 130• to 36• nm/mg/min. The amount of Ca++ which the MITO could sequester before spontaneous release was also affected by the duration of the IE and by the Ca++ in the reperfusate. Under control conditions, the MITO could readily retain i00 nm/mg protein. After 45 min IE, 50 nm/mg was the maximum Ca++ load before significant release occurred in MITO from L-Ca hearts and 25 nm/mg in the H-Ca hearts. These data suggest Ca++ overload is not responsible for MITO dysfunction accompanying an IE.
S.72