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J Kedem

Publications and source records attributed to J Kedem.

59 records · Page 4Linked to original sources

Differential effects of various inotropic agents on the intracellular NADH redox level in the in vivo dog heart.

A similar inotropic response was elicited by either increasing heart rate or infusing noradrenaline or ouabain in the open-chest dog preparation. Changes in local coronary blood supply and intracellular NADH redox level produced by these inotropic interactions were examined. Contractile tension was measured using a strain gauge arch; coronary flow, using a thermistor probe; and NADH redox level, by surface fluorometry. For each inotropic agent, isometric tension increased by about 40%. However, the mean increase in coronary flow was 80 +/- 9.7% for adrenaline, 67 +/- 18% for tachycardia, and 1 +/- 10.8% for ouabain. The mean changes in intracellular NADH redox level were -17 +/- 4.4%, 49 +/- 8.4%, and -6 +/- 6.4% for noradrenaline, tachycardia, and ouabain, respectively. The time course of changes in the various parameters was different following the onset of each inotropic stimulus. Furthermore, inducing tachycardia while the heart was under the influence of the various inotropic agents caused a reduction in contractility at different rates. These results indicate a large variation in the oxygen cost of contraction produced by these inotropic interventions, and also demonstrate notable variations in the intracellular oxygen balance. The possible relation between the intracellular NADH level and the "mechanical reserve" of cardiac muscle is discussed.

Animals↗

Nitroglycerin improves the distribution of regional oxygenation in partially ischemic canine myocardium.

The effect of nitroglycerin administration on regional oxygen supply and consumption of partially ischemic areas of myocardium was investigated in 14 open-chest anesthetized dogs. Flow in the left anterior descending coronary artery (LAD) was reduced by 50% with the aid of a specially designed screw clamp placed below the first bifurcation. Seven animals received nitroglycerin (20 micrograms/kg i.v.) 5 min following partial occlusion. The remaining animals served as controls. Regional blood flow as measured with radioactive microspheres (15 +/- 3 micron in diameter) was determined before and 10 min following partial occlusion. Regional O2 saturations in small arteries and veins were determined using a microspectrophotometric technique. Oxygen supply, A-V O2 difference, and consumption were calculated in both subepicardial and subendocardial regions of ischemic and non-ischemic myocardium after occlusion. Tissue blood flow to the partially occluded regions was reduced by about 40% in both treated and untreated animals. Nitroglycerin prevented a significant reduction in arterial and venous O2 saturation of the partially occluded region. In the occluded subendocardium, nitroglycerin reduced the skewness of the venous O2 saturation distribution. The O2 supply/consumption ratio was significantly improved by nitroglycerin in the ischemic subendocardium, compared with the same region in the control group. It is suggested that nitroglycerin improves the microregional relationship between blood flow and metabolism even in the absence of a change in total regional blood supply.

Animals↗

Regional myocardial efficiency is improved in experimental aorto-caval shunt.

We determined whether regional myocardial work efficiency (segment work/regional O2 consumption) would be elevated by surgically-augmented inflow. In 10 anesthetized open-chest dogs, shunt between the ascending aorta and the superior vena cava was used to increase cardiac output. Hetastarch (15 ml/kg) was infused before opening the shunt to maintain coronary perfusion pressure. Regional myocardial segment work and O2 consumption (MVO2) were measured, during control and two levels of elevated flow. Regional segment work (g.mm/min) was calculated as the integrated products of force (g - miniature transducer) and segment shortening (mm - ultrasonic dimension gauge) during an averaged beat expressed per minute. Local MVO2 (ml O2/min/100g) was calculated from regional blood flow (microspheres) and O2 saturations (microspectrophotometry). It was found that regional myocardial segment work increased significantly (P < 0.05) from 926 +/- 94 to 1656 +/- 220 to 1479 +/- 309 (g.mm/min) for closed, half-open, and open shunt. This increase was primarily associated with increased segment shortening (from 147 +/- 14.1 to 204.4 +/- 20.1 to 232 +/- 26.1 mm/min). Both force development and regional MVO2 were unchanged during the experiment. Regional myocardial efficiency was significantly elevated during shunt function (from 95 +/- 12 to 187 +/- 31 to 213 +/- 57 g.mm/ml O2/100g). Systolic ejection stiffness (defined as the slope of the force-length relationship during the period of ejection) decreased from 8.0 +/- 0.9 to 4.7 +/- 0.4 to 4.5 +/- 0.9 g/mm during elevated inflow. It is concluded that when cardiac work is augmented primarily by segment shortening, regional myocardial efficiency is improved. This improvement is associated with decreased resistance to shortening (stiffness).

Animals↗

Effect of beta-adrenoceptor stimulation or blockade on regional myocardial function and regional O2 consumption during myocardial ischemia.

The purpose of this study was to determine the effect of beta-adrenoceptor activation and blockade on the relationship between regional myocardial function and regional O2 consumption in ischemic and nonischemic myocardium. Myocardial regional segmental function was assessed in 28 open chest, anesthetized dogs using subepicardial dimension gauges. Ten min after LAD (left anterior descending coronary artery) occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 microgram/kg/min isoproterenol. Coronary blood flow was determined using radioactive microspheres before LAD occlusion, 10 min after occlusion, and 2 hr after LAD occlusion. Regional O2 consumption was determined using microspectrophotometry. LAD occlusion did not alter any index of myocardial function measured in the nonischemic region, but in the ischemic region, end systolic length (ESL) was increased 20% while shortening was converted to systolic bulging. No agent resulted in an improved ischemic regional function or an altered O2 consumption during LAD occlusion. In the nonischemic region the per cent shortening was increased 60% with isoproterenol compared to control. Propranolol and pindolol both increased the non-schemic regional ratio of per cent shortening vs O2 consumption significantly, suggesting an improved efficiency while isoproterenol lowered this ratio. When per cent shortening was plotted vs regional O2 consumption for all treatments, a significant linear relationship was observed in the nonischemic region. Thus, no drug treatment used in this study significantly improved central ischemic regional function, or O2 consumption, but both beta-adrenoceptor blockers seemed to result in an improved relationship between segmental shortening and O2 consumption in the nonischemic region.

Adrenergic beta-Agonists↗

Novel design of a regional myocardial force transducer.

A novel force transducer was designed to measure the circumferential regional force developed in the ventricular myocardium in vivo. The transducer is composed of a frame, a carrier bar, and a cantilever spring. Two resistance strain gauges embedded on the spring serve as force-sensing elements. The output of a Wheatstone-bridge circuit, containing these two gauges and a temperature compensation resistor, is connected to a preamplifier. The main advantages of this prototype include the initial stretch-adjustment ability (physiologic 0) low temperature drift, high linearity (r = 0.99) with loads ranging from 0 to 100 g, and moderate sensitivity of 0.232 mV/V/g at room temperature. The transducer was validated with in-vivo canine experiments. The experimental results showed that this transducer can be used to reliably measure the myocardial force development during altered cardiac conditions, such as myocardial stunning and myocardial ischemia.

Animals↗