Biomedical subjects

J Kedem

Publications and source records attributed to J Kedem.

At least 37 records · Page 2Linked to original sources

PubMed1990

Pacing during reperfusion elevates regional myocardial oxygen consumption.

Reperfusion after 2 h of coronary artery occlusion has been shown to result in depressed coronary blood flow to the reperfused region and elevated regional myocardial extraction. This suggests that reperfused myocardium, even after 4 h of reperfusion, possesses limited flow and O2 consumption reserves. We studied the capacity of reperfused myocardium to elevate regional blood flow and regional O2 consumption in response to sustained increased O2 demand, produced by atrial pacing. Two groups of anesthetized open-chest dogs were subjected to 2 h of left anterior descending coronary artery occlusion followed by 4 h of reperfusion. One group was subjected to atrial pacing (40% increase in heart rate) during the entire 4-h reperfusion period. Regional O2 saturation was measured by microspectrophotometry in samples of reperfused and nonoccluded subepicardium and subendocardium, which were taken at the end of the reperfusion period. In the paced group, regional blood flow (radiolabeled microspheres) to reperfused myocardium was significantly higher than to corresponding regions of unpaced hearts (110 +/- 22 vs. 40 +/- 9 ml.min-1 x 100 g-1 in the subendocardium). In the control group, O2 extraction of reperfused subendocardium was significantly higher than that measured in the corresponding nonoccluded region (11.0 +/- 0.9 vs. 8.0 +/- 0.6 ml O2/100 ml). Pacing did not elevate O2 extraction of reperfused myocardium (8.7 +/- 0.6 vs. 8.3 +/- 0.7 ml O2/100 ml). Myocardial O2 consumption was significantly elevated in all regions of the paced heart. It is concluded that reperfused myocardium possesses significant unutilized O2 supply and consumption reserves.

Animals↗

PubMed1989

Relationship between local oxygen consumption and local and external cardiac work: effect of tachycardia.

This study was designed to determine the extent of coupling between regional myocardial segment work and corresponding regional oxygen consumption, and to examine whether tachycardia induced changes in regional work are translated into corresponding changes in external cardiac work. In the open chest anaesthetised dog, the heart was paced at frequencies of 120-270 beats.min-1. Global and regional myocardial O2 supply, consumption, and balance were evaluated at each heart rate, and correlated with corresponding functional changes. Global cardiac function was evaluated from aortic flow, blood pressure, and left ventricular pressure. Coronary sinus flow and O2 saturation were used to calculate O2 consumption. The integrated multiple of myocardial shortening (ultrasonic dimension crystals) by corresponding force (strain gauge arch) during an averaged beat was used to express regional segment work. Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry was used to evaluate O2 saturation in small arteries and veins. These indices were used to calculate regional myocardial oxygen consumption. NADH redox levels were recorded by surface fluorometry, and were found to increase with heart rate by up to 67%. Increasing heart rate from 120 to 180 beats.min-1 increased regional work from 3040(SEM 220) to a peak of 4290(280) mm.g-1.min-1, whereas external cardiac work did not increase [67.0(2.6) to 65.3(4.4) mm Hg.litre-1.min-1] and fell further at the highest rates. Regional oxygen consumption increased from 6.16(0.47) to 8.29(0.53) ml O2.min-1.100 g-1 and was linearly related to regional work at all heart rates (r = 0.971, p less than 0.05). External cardiac work fell by about 26% whereas global myocardial oxygen consumption increased by 49% during tachycardia. It is concluded that myocardial oxygen consumption is more closely related to regional segment work than to external work, and that tachycardia significantly raises the oxygen cost of external work of the heart.

Animals↗

PubMed1989

Effect of diltiazem on regional oxygenation of reperfused myocardium.

Reperfusion after 2 hr of experimental ischemia results in reduced blood flow to the reperfused region, as well as elevated regional O2 extraction in that region. The aim of the present study was to determine whether diltiazem, administered during reperfusion, can improve regional blood flow and lower O2 extraction in the previously occluded region. In open-chest anesthetized dogs, 2-hr occlusion of the left anterior descending coronary artery was followed by a 4-hr period of reperfusion. In 7 of the 15 animals, diltiazem (0.45 micrograms/kg/min) was infused i.v. during the reperfusion period; this was preceded by a loading dose of 0.18 micrograms/kg 10 min before release. Small artery and vein O2 saturations obtained microspectrophotometrically were combined with regional blood flow measurements using radioactive microspheres to determine regional myocardial O2 consumption. In both groups, coronary occlusion lowered regional flow to a similar level. After a 4-hr reperfusion, flow to the subendocardial region of treated hearts was significantly greater than that to the untreated reperfused myocardium (75.6 +/- 46.4 vs. 40.3 +/- 25.8 ml/min/100 g), and did not differ from the preocclusion level. The subendocardium/subepicardium flow ratio was reversed in occluded and untreated reperfused myocardium (subendocardium flow less than subepicardium flow), but was not reversed in treated reperfused regions. Myocardial oxygen extraction was 11.0 +/- 2.4 ml of O2/100 ml of blood in the untreated reperfused subendocardium, and was significantly decreased to 8.5 +/- 0.9 ml of O2/100 ml in the treated subendocardium. The proportion of individual veins having O2 saturations below 25% was significantly reduced by diltiazem treatment from 45.2 to 22.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Beta-adrenoceptor stimulation and blockade during myocardial ischemia in dogs: effect on cardiac O2 supply and consumption.

The effect of beta-adrenoceptor blockade and activation on ischemic regional and microregional myocardial O2 supply/consumption parameters was assessed in 28 open chest, anesthetized dogs. Ten minutes after LAD occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 microgram/kg per min isoproterenol. Coronary blood flow was determined using radioactive microspheres before and 2 h after LAD occlusion while O2 supply/consumption parameters were determined using microspectrophotometry. Ischemia resulted in a 66% reduction in subendocardial flow in controls in the ischemic zone and no experimental treatment significantly altered this flow. Pindolol resulted in a significant improvement in the ischemic regional subendocardial/subepicardial flow ratio (from 0.69 in the control ischemic region to 0.88 during pindolol treatment). O2 extractions were significantly increased and O2 consumptions were significantly depressed in the ischemic regions of all groups. O2 extractions were increased to a lesser degree in the ischemic region with the use of pindolol and propranolol. Propranolol and pindolol both significantly decreased the proportion of veins with low (0-20%) O2 saturations in the ischemic region indicating an improved microregional distribution of blood flow and/or O2 consumption within the ischemic region.

Adrenergic beta-Agonists↗

PubMed1987

Specific effects of nitroprusside on myocardial O2 balance following coronary ligation in the dog heart.

The effect of gradual infusion of nitroprusside was studied in healthy and in ischemic hearts. In two areas of the left ventricular surface (ischemic and non-ischemic) local coronary blood flow was measured by a thermistor technique. Isometric contractile tension was recorded with strain gauge arches, and nicotinamide-adenine-dinucleotide (NADH) redox state was measured simultaneously in both regions using a two-channel fluorometer. Aortic blood pressure was also recorded. It was found that at an infusion rate of 1.0 microgram/kg/min, nitroprusside increased regional coronary blood supply in the healthy heart as well as in the ischemic and nonischemic areas of left anterior descending artery (LAD)-ligated hearts. Flow elevation was similar in all regions (37.0 +/- 6.1, 42.5 +/- 13.5 and 45.36 +/- 14.8%, respectively). At higher doses, a decrease of 6-10% in blood pressure had a detrimental effect on the coronary flow to the ischemic region without reducing flow to the nonischemic region. The NADH redox level was not significantly improved by nitroprusside in spite of elevated coronary blood supply to all regions examined. Moreover, higher doses of nitroprusside resulted in a significant elevation in NADH levels that could be correlated to the decrease in blood pressure. It is concluded that the effect of nitroprusside on coronary blood supply and myocardial O2 balance may be strongly dependent on the magnitude of its effect on blood pressure.

Animals↗

PubMed1986

Variations in left and right ventricular oxygen balance produced by paired electrical stimulations.

The possible differential effect of positive inotropic stimulation upon regional myocardial oxygen balance in the two ventricles was investigated during tachycardia and paired electrical stimulation. Isometric contractile force was measured by strain gauge arches; local coronary blood supply was measured by thermistor probes and intracellular NADH redox level was recorded using surface fluorometry. It was found that when contractility was increased by paired stimulation at a basic rate of 140 bpm, the inotropic response was more pronounced in the right ventricle (97.2 +/- 11.5%) than in the left (63.1 +/- 12.6%). Coronary blood supply to the left ventricle increased by 117.8 +/- 30.4% and the corresponding NADH redox level increased by 54.3 +/- 19.9%. When the contractile force was increased to the same extent (64.1 +/- 8.9%) by single stimulation at a rate of 210 bpm, the coronary flow to the left ventricle was increased by only 36.4 +/- 11.0% and the NADH state rose by 67.1 +/- 12.1%. It is concluded that paired stimulation reduced the mechanical limitation to flow during tachycardia, thus allowing coronary blood supply to increase in response to positive inotropic stimulation, thereby preserving a relatively improved oxygen state. It was also observed that the ratio contractile force/blood supply (contraction efficiency) was usually proportional to the NADH redox level (oxygen balance). Nevertheless, variations observed in the force/supply ratio for the left ventricle indicate that the NADH redox level cannot be predicted quantitatively by the force/supply ratio.

Animals↗

PubMed1986

Effect of coronary vasodilators and pacing upon regional oxygen balance of the ischaemic myocardium.

In anaesthetized open-chest dogs, regional contractile force, epicardial tissue blood flow, and local NADH redox levels were recorded during graded ventricular pacing in the range 150-285 bpm. These parameters were measured before, and 30 min following LAD coronary artery occlusion. It was found that during pacing, blood supply to the untreated ischaemic region was reduced by 65.4 +/- 11% of control values at a rate of 150 bpm, and fell to -105 +/- 40.2% at a rate of 225 bpm. Hypopneic respiration prevented this pacing induced flow reduction. Pacing in the presence of nitroglycerin resulted in a marked increase in regional flow. Similarly, the vasodilator treatments prevented the marked elevation in NADH levels (77.5 +/- 15.6%) produced by pacing in the untreated ischaemic myocardium. The reduction in regional contractile force in the ischaemic region produced following pacing (-30.5%) was reversed during both vasodilator treatments (+47.2% during nitroglycerin and +23.4% during hypopnea). It was concluded that vasodilation improves regional ischaemic myocardial oxygen balance, thus expanding the functional reserve of the ischaemic muscle. Nitroglycerin is more active.

Animals↗

PubMed1986

Relation between myocardial substrate utilization, oxygen consumption and regional oxygen balance in the dog heart in vivo.

The interaction between myocardial function, oxygen consumption and energy production was examined in the left ventricular myocardium during various physiological conditions. Myocardial function was measured by both LV dP/dTmax and by local contractile tension. Coronary blood flow was measured from the coronary sinus; regional coronary blood supply was recorded using a thermistor placed on the epicardial surface. Intracellular oxygen balance was estimated using NADH fluorescence. Myocardial oxygen consumption and utilization of glucose, pyruvate, lactate and free fatty acids were calculated from their concentrations in the arterial and coronary sinus blood. The effects of tachycardia at 180 and 240 bpm, noradrenaline infusion (25 micrograms kg-1 min-1), and increased coronary blood flow caused by hypopneic respiration were examined. During pacing, contractile force, coronary flow and NADH fluorescence increased. At 240 bpm, the lactate/pyruvate ratio increased from 5.98 +/- 0.92 to 8.76 +/- 1.41 and NADH fluorescence increased from 50 to 71.7 +/- 3.73 (as compared to control), indicating impairment of myocardial oxygenation. Hypopneic respiration produced a marked elevation of coronary blood flow. Both noradrenaline infusion and hypopnea produced a decrease in both NADH fluorescence and the lactate/pyruvate ratio. No significant difference was found between the FORCE/ATP, FORCE/MVO2 and ATP/MVO2 ratios during pacing and noradrenaline. However, during hypopnea, the amount of ATP apparently formed (as calculated by substrate utilization assuming the formation of 3 ATP molecules per oxygen) was disproportionately greater than contractile force and oxygen consumption. It is suggested that this discrepancy may be due to the uncoupling of oxidative phosphorylation.

Adenosine Triphosphate↗

PubMed1985

Improvement in regional myocardial O2 supply and O2 consumption by nitroglycerin during ischemia.

In eight open-chest anesthetized dogs, nitroglycerin (10 micrograms/kg per min) was infused intravenously for 2 h, beginning 10 min following ligation of the left anterior descending coronary artery. Oxygen supply, (radioactive microspheres), extraction (microspectrophotometry) and consumption were determined in subepicardial and subendocardial regions of both ischemic and non-ischemic myocardium, and compared to eight control hearts. In control, coronary occlusion reduced both subepicardial and subendocardial blood flow by 49.5% and 79.5% respectively. In the presence of nitroglycerin, depression of blood flow to the occluded regions was significantly less marked (-79.5% in control and -26.6% in the nitroglycerin group in the subendocardium). O2 extraction was significantly lowered by nitroglycerin in all areas. Regional O2 consumption was significantly lower in the control occluded than non-occluded regions; no regional O2 consumption differences were observed following nitroglycerin. In the occluded regions, nitroglycerin reduced the number of veins with very low O2 saturation. It is concluded that nitroglycerin improves the O2 supply/consumption balance in ischemia by redistribution of blood flow and possibly by alterations in local O2 consumption.

Animals↗

PubMed1985

Effect of global vs regional ischaemia upon myocardial contractility and oxygen balance.

The possible role of catecholamines upon the nature of myocardial response to regional and global left ventricular ischaemia was investigated. Global ischaemia was accomplished by temporary occlusion of the left main coronary artery and regional ischaemia by temporary ligation of the left anterior descending coronary artery. Isometric force of contraction was measured with strain gauge arches, regional blood flow by a thermistor technique and intracellular NADH redox level by a fluorometric technique. These measurements were made simultaneously in two areas on the left ventricular myocardium: one immediately below the bifurcation of the LAD and the other immediately below the circumflex coronary artery. Following LAD occlusion a variable inotropic response was observed in the ischaemic area. A decrease in contractile tension was found in 19 of the dogs (44%), no change in 23% and an increase was found in 33%. Global ischaemia invariably resulted in a decrease in contractile tension. NADH redox state was markedly higher during global than during regional ischaemia. Propranolol administration blocked the positive inotropic response to regional ischaemia. It is concluded that endogenous catecholamine release may be responsible for increased contractile force during regional ischaemia. This response is apparently limited by the oxygen availability to the tissue.

Animals↗

PubMed1985

Preservation of myocardial oxygen balance and functional reserve by coronary vasodilators.

Reduced myocardial function at very high heart rates may be due to limited coronary blood supply. The effects of the vasodilators nitroglycerin (10 micrograms kg-1 min-1) and elevated CO2 upon regional function during tachycardia were studied. In open-chest anaesthetized dogs, regional contractile force, epicardial tissue blood flow and local NADH redox level were recorded during graded ventricular pacing. It was found that the vasodilating action of nitroglycerin in the unpaced heart was much lower than produced by CO2 (23.6 +/- 5.8% vs. 137.6 +/- 33.5%). Maximal pacing at 275 bpm caused only a moderate flow elevation in control (20 +/- 6.8%) and CO2 conditions (20.3 +/- 4.03%), but marked vasodilation during nitroglycerin infusion (85.2 +/- 14.6%). Regional function during tachycardia was improved similarly by both vasodilators. NADH levels increased with heart rates under all experimental conditions, but the absolute NADH levels were consistently lower following vasodilator treatments. The lowest NADH levels were observed during nitroglycerin treatment at all heart rates. It is suggested that nitroglycerin augments myocardial functional reserve by preserving oxygen balance more than predicted by its vasodilatory effect alone.

Animals↗

PubMed1982

Real time data acquisition and analysis of cardiovascular experiments in dogs.

A hardware-software system is described which enables physiologists to utilize the DEC PDP-ll computer for data acquisition and analysis in the real-time experimental environment. The system allows for A/D conversion of up to 16 physiological parameters, as well as various calculations based upon these parameters such as heart rate, cardiac work, and derivatives and integrals of ventricular tension and pressure. By using a push-button box, the investigator can request a display of the parameters just acquired, a graphic display summarizing the results of the experiment up to the time of request, and also change various parameters such as gain factors, names of stages and erasures. At the end of the experiment, the computer prints a table summarizing the course of the experiment. A data file is written in a standardized format containing the essential data obtained during the experiment.

Animals↗

PubMed1982

Effect of local ischaemia on the myocardial oxygen balance and its response to heart rate elevation.

The capacity of ischaemic myocardium to respond to the inotropic stimulus of tachycardia was investigated in open-chest anaesthetized dogs following ligation of a branch of the anterior descending coronary artery. In two areas of the left ventricular surface (ischaemic and non-ischaemic), local coronary blood flow was measured by thermistors and isometric contractile force was recorded with strain gauge arches. NADH redox state was measured simultaneously in both regions using a two-channel surface fluorometer. It was found that ligation was followed by an immediate fall in local coronary blood flow to the ischaemic region, accompanied by a sharp elevation in NADH redox level. Local contractile force in the ischaemic region was also reduced. The non-ischaemic region showed little or no change following occlusion. Response to heart rate elevation before ligation was increased work, elevation of NADH redox levels, and increased coronary flow. Following ligation, this response was attenuated in the ischaemic region, but not abolished. It is concluded that ischaemic myocardium retains the capacity for inotropic response even when intracellular O2 levels are low.

Animals↗

PubMed1981

Dynamic redistribution of coronary blood flow in the dog as measured by a thermistor technique.

The effect of heart rate upon the coronary blood supply to the right and left ventricles was studied in anaesthetized, open-chest dogs. Indirect recording of coronary supply was obtained using thermistors placed locally on the surface or in the wall of the ventricles. The validity of the thermistor technique was examined in vivo as well as by using an in vitro laboratory model. Myocardial perfusion was also measured using electromagnetic flowmeters placed around the anterior descending and circumflex arteries, as well as the coronary sinus and Thebesian drainage. It was found that at heart rates lower than about 150/min, coronary perfusion to all areas increased equally as rate was elevated. At higher heart rates, coronary flow to the right ventricle continued to increase linearly with rate, whereas perfusion to the left ventricle either increased much less or declined. It is concluded that tachycardia causes coronary flow to be dynamically redistributed in favour of the right ventricle.

Animals↗

PubMed1981

An experimental approach for evaluation of the O2 balance in local myocardial regions in vivo.

Quantitative evaluation of myocardial oxygen balance can be accomplished by measurement of oxygen supply, demand, and intracellular oxygen concentration. Experimentally, these parameters are often related to coronary blood flow, cardiac contractility, and mitochondrial NADH redox level, respectively. Methods were developed to measure these three parameters in a local region on the myocardial surface in open-chest dogs. Local coronary blood supply was measured with the aid of a small surface thermistor, and cardiac work with a miniature strain gauge arch. NADH oxidation--reduction state was recorded using surface fluorometry through a fibre optic light guide. Transient anoxia produced by nitrogen breathing caused a rapid but reversible elevation in NADH levels, which was not always accompanied by a concomitant change in contractile force. Elevation of heart rate resulted in a rise in intramitochondrial NADH followed by an increase in coronary flow. In spite of the increased flow, NADH levels remained elevated, indicating a change in the O2 balance; this may indicate that autoregulation does not necessarily result in total compensation.

Animals↗

PubMed1981

Coronary vasodilation produced by tachycardia under various basal flow conditions.

Some properties of coronary vasodilation produced by heart rate elevation under various basal coronary flow levels was studied. Coronary sinus blood flow, myocardial oxygen consumption and left ventricular contractile force were measured in anaesthetized, open-chest dogs. Heart rate was progressively increased by electrical stimulation at rates ranging from 60/min to 210/min. This was repeated during control, noradrenaline infusion (0.2 microgram kg-1 min-1), in the presence of propranolol (0.25 mg/kg), and during hypopneic positive pressure respiration. It was found that under all experimental conditions, coronary perfusion increased linearly with heart rate. At each rate, coronary flow was greater during noradrenaline infusion and hypopneic respiration than that observed during control or following beta-blockade. Myocardial oxygen consumption behaved similarly to flow, and MVO2 was lowest in the presence of propranolol, and highest during hypopneic ventilation and catecholamine infusion. Contractile force per min (heart rate x tension) also increased with increasing heart rate, but was greatest during noradrenaline infusion, lowest during beta-blockade, and similar during both control and hypopneic respiration. These results indicate that the oxygen cost of contraction was different under the various conditions, and was particularly wasteful during hypopneic respiration. It is concluded that autoregulation caused by heart rate elevation is not dependent on the initial state of coronary blood flow, and that endogenous catecholamine release cannot account for this phenomenon.

Animals↗

PubMed1981

Effect of coronary vasodilation produced by hypopnea upon regional myocardial oxygen balance.

An attempt was made to differentiate between autoregulatory coronary vasodilation and changes in vasomotor tone produced by factors extrinsic to the heart. this was done by investigating the relation between local cardiac force and local coronary blood supply. Intracellular NADH redox levels were also measured in order to further elucidate the oxygen balance under various experimental conditions. In anaesthetized open-chest dogs, local blood supply was estimated with the aid of a thermistor probe, and the oxidation-reduction state of mitochondrial pyridine nucleotide was measured by a surface fluorometric technique. Local myocardial contractile force, as well as blood pressure and ECG were recorded simultaneously with the above parameters. The heart was paced at frequencies from 60/min to 300/min with an electronic stimulator, under both normoxic and hypopneic conditions. It was found that elevation of heart rate caused a progressive increase in local blood flow during both normal and hypopneic ventilation. The absolute flow values during hypopnea were approximately double those during normoxia. Heart rates above 120/min or 150/min resulted in a progressive increase in NADH fluorescence. This response to elevated heart rate was less prominent or absent during hypopnea. Contractile force during hypopnea was greater at elevated heart rates than during normal breathing. Data are brought which suggest that whereas vasodilation following increased heart rate is probably due to an autoregulatory mechanism, the marked vasodilatatory effect of hypopnea is related to elevated arterial CO2 levels. It is suggested that hypercapnia markedly stimulates extrinsic coronary vasodilation thereby supplying enough oxygen to maintain contractility even at very high heart rates. Moreover, intracellular O2 concentration (mitochondrial NADH level) is maintained at a normal level despite the greatly increased demand.

Animals↗

PubMed1980

Effect of reserpine upon the haemodynamic course of recovery following experimental myocardial infarction.

Acute haemodynamic consequences of coronary artery ligation were evaluated in twenty-four anaesthetized open-chest dogs, nine of which were pretreated with reserpine. The following parameters were measured before, and at 15-min intervals following ligation for at least five hours : ECG, mean arterial blood pressure, aortic blood flow, left ventricular pressure, heart rate, peripheral resistance (P.R.), end-diastolic pressure, dP/dtmax, and "internal work" (I.W. = heart rate x dP/dtmax). It was found that aortic flow was similar in control and reserpine-pretreated dogs (753 +/- 43 vs. 744 +/- 57 ml/min respectively), even though heart rate, blood pressure and other parameters were significantly higher in the control animals. Furthermore, the controls could be divided into two groups : recoverers (R) and non-recoverers (N), on the basis of late stage haemodynamic differences. The ratio of PR/IW taken within one hour of ligation was significantly higher in the R group (496 +/- 69) and reserpine group (479 +/- 30) than in the N group (242 +/- 28), and could predict course of recovery in each dog studied. It is concluded that the presence of myocardial catecholamines may be deleterious to the ischemic heart when the PR or IW are disproportionately altered.

Animals↗