Biomedical subjects

J Kedem

Publications and source records attributed to J Kedem.

At least 19 recordsLinked to original sources

PubMed2005

Characteristic dysfunction of stunned myocardium induced by 2,3-butanedione monoxime without ischaemia.

1. In the present study, we tested the hypothesis that, even in the absence of prior ischaemia, 2,3-butanedione monoxime (BDM), an inhibitor of contraction at the actin-myosin level, could produce the postischaemic dysfunction characteristic of stunned myocardium. 2,3-Butanedione monoxime was injected directly into the left anterior descending coronary artery (LAD) before and again after myocardial stunning produced by 15 min occlusion of the LAD followed by 30 min reperfusion. 2. Regional myocardial force, segment shortening and regional work were measured in both the LAD-perfused area and the area perfused by the circumflex coronary artery, which served as a control area. Regional dysfunction produced by BDM injection or ischaemia-reperfusion was assessed quantitatively by five parameters: end-diastolic length (EDL), shortening onset delay (delay), systolic bulge (bulge), end-shortening time delay (EST) and tail work ratio (TWR). 3. It was found that injection of BDM into the LAD caused dyskinesis similar to that caused by occlusion-reperfusion. Both displayed elevated EDL and marked increases in delay, bulge, EST and TWR; these parameters were significantly higher in the dyskinesis caused by BDM injection. Despite dysfunctional fibre shortening, intracoronary BDM injection did not reduce regional force. 4. Thus, BDM can elicit changes similar to those characteristic of postischaemic dysfunction. Because contractility was not impaired, dysfunction was apparently caused by disrupting the association between contractile force and muscle motion.

Acetylcholine↗

PubMed2001

Hypervolaemia improves global and local function and efficiency in postischaemic myocardium.

1. In the present study, we investigated the effects of blood volume on postischaemic function and efficiency. In 14 anaesthetized dogs, following recovery from a period of 15 min occlusion of the left anterior descending coronary artery, the effects of hypervolaemia (HYPER; 15% increased volume produced by fast infusion of Hespan; B Braun Medical, Irvine, CA, USA), normovolaemia (NORMO) and hypovolaemia (HYPO) were studied. 2. Although myocardial O2 consumption was not significantly increased by volume (6.37+/-0.94 vs 6.89+/-1.1 mL/min per 100 g for HYPO and HYPER, respectively), local work of the stunned myocardium was markedly elevated (8.8+/-1.7 vs 22.5+/-3.5 g.mm/ beat, for HYPO and HYPER, respectively; P < 0.05). External work of the heart was also significantly improved (71.8+/-12.7 vs 139.5+/-16.2 mmHg.L/min for HYPO and HYPER, respectively). These data indicate markedly improved efficiency produced by volume, because work was increased with no change in myocardial O2 consumption. 3. Local dysfunction was characterized by several parameters, including systolic bulge, end-diastolic length, delay to onset of shortening, end shortening time delay (EST) and tail work ratio. Hypervolaemia reduced EST compared with hypovolaemia (98.6+/-18.3 vs 110.7+/-14.9 msec, respectively; P < 0.05) and improved tail work ratio (28.0+/-7.0 vs 36.0+/-7.0%, respectively; P < 0.05), with no effects on systolic bulge, end-diastolic length and delay to onset of shortening. 4. Thus, even in the postischaemic myocardium, increasing work by volume is energetically efficient and is accompanied by partial improvement of local dysfunction.

Animals↗

PubMed1998

Beta-adrenergic stimulation of reperfused myocardium after 2-hour ischemia.

Postischemic myocardium possesses considerable contractile and metabolic reserves, but their mobilization could result in increased cell death. We tested the hypothesis that beta-adrenergic stimulation of reperfused myocardium would increase segment work more than O2 consumption, thereby improving efficiency without increased cell death. In 16 open-chest anesthetized dogs, the left anterior descending coronary artery (LAD) was ligated for 2 h; during the reperfusion period, isoproterenol (ISO; 0.1 microg/kg/min, i.v.) was administered to nine of the animals. Regional myocardial segment length and force were measured in the anterior (LAD) and posterior circumflex coronary artery (CFX) regions of the left ventricular myocardium. Work was calculated as the integrated products of force and shortening for each region. Regional myocardial O2 consumption was obtained from LAD flow and arterial and local venous O2 saturations. Infarct size (tetrazolium) was measured in the treated and untreated hearts at the end of the experiment. In untreated hearts, the first derivative of left ventricular pressure, cardiac output, and external work were significantly depressed during reperfusion; ISO restored all values to preocclusion levels. Regional myocardial work in both LAD and CFX regions was significantly increased by ISO (from 564 +/- 207 to 1,635 +/- 543 g/mm/min in LAD, and from 753 +/- 90 to 1,426 +/- 245 g/mm/min in CFX). Efficiency (work/oxygen consumption) of the reperfused region was similarly increased. LAD flow was significantly increased by ISO, and O2 extraction was unchanged. Infarct size was 28.2 +/- 4.7% in untreated hearts and 29.0 +/- 3.5% in ISO hearts. Thus isoproterenol stimulation significantly improved both regional and global function without subsequent evidence of increased cell death.

Adrenergic beta-Agonists↗

PubMed1997

Local inotropic stimulation by methylene blue does not improve mechanical dysfunction due to myocardial stunning.

We tested the hypothesis that reduction of intramyocardial cyclic guanosine monophosphate (GMP) by methylene blue (MB) would improve mechanical dysfunction in stunned myocardium. Regional stunning was produced in nine open-chest anesthetized dogs by a 12-min left anterior descending coronary artery (LAD) occlusion. MB was infused into the LAD during reperfusion (1 mg/kg per min). Stunning reduced LAD force development, introduced a significant time delay between the onset of force and shortening (delay) and caused significant systolic bulging to occur. Stunning reduced systolic regional work (the integrated product of force and segment shortening during systole), but did not significantly alter regional oxygen consumption or cyclic GMP levels. MB decreased cyclic GMP (1.8 +/- 0.2 to 0.9 +/- 0.1 pmol/g) and increased peak force (36 +/- 5 to 55 +/- 10 g). However, MB increased delay (93.9 +/- 18.4 to 233 +/- 19 ms) and systolic bulging (5.9 +/- 2.1% to 9.3 +/- 2.8%) and further reduced systolic regional work (control; 4204 +/- 933 g x mm/min; stunned: 2191 +/- 542 g x mm/min; MB: 1153 +/- 516 g x mm/min). MB increased regional myocardial oxygen consumption (7.4 +/- 1.0 to 15.6 +/- 2.7 ml O2/min per 100 g). These results suggest that depressed contractility, while present in myocardial stunning, is not the primary cause of mechanical dysfunction.

Animals↗

PubMed1996

Effect of cyclic GMP reduction on regional myocardial mechanics and metabolism in experimental left ventricular hypertrophy.

We tested the hypotheses that decreased myocardial cyclic GMP levels produced by intracoronary injection of methylene blue would increase local myocardial work and O2 consumption while decreasing intracellular cyclic GMP and that the relation between work, O2 consumption, and cyclic GMP may be altered in left ventricular hypertrophy (LVH) produced by aortic valve plication. In 8 control and 8 LVH open-chest anesthetized dogs, 1 mg/kg/min methylene blue was infused into the left anterior descending coronary artery (LAD); the circumflex region (CFX) served as control area. Regional work was calculated as the integrated product of force (miniature transducer) and segment shortening (sonomicrometry). Regional myocardial O2 consumption was calculated from flow measurements (radioactive microspheres), and regional O2 saturations (microspectrophotometry). A radioimmunoassay was used to determine intracellular level of cyclic GMP in the myocardium. Global hemodynamics and blood gases were unchanged by methylene blue in both control and LVH animals. Intracoronary methylene blue increased regional work from 762 +/- 129 to 1,451 +/- 307 g center dot mm/min in controls and from 912 +/- 173 to 1581 +/- 253 g center dot mm/min in the LVH groups. No significant changes in CFX regional work were observed. Regional blood flow, O2 extraction, and O2 consumption remained unchanged after injection of methylene blue in both control and LVH animals. The basal levels of cyclic GMP in the LVH group were fivefold higher than that in controls. In both groups, cyclic GMP levels were significantly decreased by methylene blue and to a greater extent in the LVH animals (from 6.16 +/- 1.2 to 3.34 +/- 0.44 pmol/g) than in the control animals (from 1.32 +/- 0.20 to 1.09 +/- 0.19 pmol/g). Therefore, intracoronary methylene blue increased regional myocardial work equally in control and LVH hearts without affecting regional metabolism (i.e., increased efficiency). For the same increased mechanical function, the hypertrophic myocardium exhibited a greater reduction in cyclic GMP pool size.

Animals↗

PubMed1996

Modeling of mechanical dysfunction in regional stunned myocardium of the left ventricle.

Reversible mechanical dysfunction of the myocardium after a single or multiple episode(s) of coronary artery occlusion has been observed in previous studies and is termed myocardial stunning. The hypothesis that stunning could be represented by a decrease in maximum available muscle force in the stunned region was examined by means of a mathematical model that incorporates series viscoelastic elements. A canine experimental model was also employed to demonstrate depressed contractility and a consistent delay of shortening in the stunned region. The mechanical model of the left ventricle was designed to include a normal and stunned region, for which the stunned region was allowed to have variable size. Each region consisted of a volume and time dependent force generator in parallel with a passive elastic force element. The passive elastic element was placed in series with a constant viscosity component and a series elastic component. The model was solved by means of a computer. Passive and active properties of each region could be altered independently. The typical regional measures of muscle performance such as percent shortening, percent bulge, percent thickening, delay of shortening, percent increase in end-diastolic length and other hemodynamic measures were computed. These results were similar to those observed in animal models of stunning. In addition, a nearly linear relationship with end-diastolic length and delay of shortening was predicted by the model. It was concluded that a decrease in the peak isovolumic elastance and augmentation of viscosity effect of creep during stunning can explain mechanical abnormalities of stunned myocardium.

Analysis of Variance↗

PubMed1996

Action of acetylcholine on regional myocardial work and metabolism in vivo: association with cyclic GMP.

This study was designed to test the hypothesis that in the in vivo dog heart, increases in cyclic (c) GMP and also decreases in cAMP induced by intracoronary administration of acetylcholine are associated with depressed myocardial function. In 10 open-chest anesthetized dogs, 0.5 microgram.kg-1.min-1 of acetylcholine was infused into the left anterior descending coronary artery. The intracoronary infusion of acetylcholine was continued simultaneously with 0.1 microgram.kg-1.min-1 of isoproterenol. Regional segment work was calculated as the integrated product of force (auxotonic force transducer) and segment shortening (sonomicrometry). Regional myocardial O2 consumption was calculated from blood flow measurements and regional O2 saturations. Competitive radioligand binding assays were used to determine the intracellular level of cAMP and cGMP in the myocardium. Local intracoronary infusion of acetylcholine significantly reduced regional segment work (from 36.7 +/- 6.5 to 19.1 +/- 3.7 x 10(-3) J/min) and O2 consumption (from 6.4 +/- 0.8 to 3.8 +/- 0.7 mL O2.min-1.100 g-1). This was related to a decrease in cAMP levels (from 364 +/- 25 to 262 +/- 17 pmol/100 g) and an increase in cGMP levels (from 1.34 +/- 0.06 to 1.78 +/- 0.15 pmol/100 g). When isoproterenol (0.1 microgram.kg-1.min-1) was added to the acetylcholine infusion line, cAMP levels tripled to 769 +/- 84 pmol/100 g, while O2 consumption rose to 6.6 +/- 1.4 mL O2.min-1.100 g-1. However, regional work was only partially restored (25.7 +/- 4.8 x 10(-3) J/min). Thus, both cAMP decrements and cGMP elevation occurred together with the negative inotropic effect of acetylcholine, and increased cAMP alone (produced by isoproterenol) did not fully overcome the acetylcholine effect. This was associated with elevated intracellular levels of cGMP.

Acetylcholine↗

PubMed1995

Reduced effect of phenylephrine on regional myocardial function and O2 consumption in experimental LVH.

In a dog model of left ventricular hypertrophy (LVH) created by aortic valve plication, we examined the hypothesis that regional myocardial inotropic and metabolic responses to alpha-adrenergic stimulation would be diminished due to decreased alpha-adrenoceptor number. After systemic beta-adrenergic blockade, phenylephrine (PE, 5 micrograms.kg-1.min-1) was infused into the left anterior descending artery in eight LVH and nine control open-chest anesthetized dogs. The circumflex region served as control. In both regions, local segment work was calculated as the integrated products of force (miniature transducer) and segment shortening (ultrasonic crystals). Local myocardial O2 consumption was calculated from regional blood flow (microspheres) and O2 saturation (microspectrophotometry). A saturation radioligand binding assay was used to determine adrenoceptor number and affinity. In control animals in the treated region, PE increased work from 815 +/- 140 to 1,493 +/- 149 g.mm.min-1. In LVH, work was not significantly altered (688 +/- 142 vs. 730 +/- 149 g.mm.min-1). Regional blood flow was elevated in controls (81 +/- 10 to 141 +/- 24 ml.min-1.100 g-1) but was not changed in LVH (105 +/- 12 vs. 123 +/- 18 ml.min-1.100 g-1). In controls, but not in LVH, myocardial O2 consumption was almost doubled during PE infusion (6.2 +/- 0.9 vs. 12.0 +/- 2.1 ml O2.min-1.100 g-1). alpha-Adrenoceptor number and dissociation constants values were not different between control and LVH (15.7 +/- 2.8 vs. 16.4 +/- 2.7 fmol/mg protein; 13.2 +/- 3.4 vs. 16.9 +/- 4.3 nm, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effect of intracoronary nitroprusside on cyclic GMP and regional mechanics is altered in a canine model of left ventricular hypertrophy.

Nitroprusside can produce negative inotropy by activating cGMP. We hypothesized that in left ventricular hypertrophy produced by aortic valve plication (LVH), control of myocardial work and metabolism by cGMP production would be altered in response to nitroprusside. In anesthetized open chest preparations using 9 LVH and 12 control dogs, nitroprusside (4 micrograms/kg/min) was infused into the left anterior descending coronary artery. The circumflex (CFX) region served as an internal control. Segment force (miniature gauge) and length (sonomicrometer) were measured in both regions. Segment work was calculated as the integrated products of local force and segment shortening. Regional myocardial O2 consumption was calculated from blood flow measurements (radioactive microspheres) and regional O2 saturations (microspectrophotometry). Radioimmunoassay was used to determine regional cGMP levels. In control dogs, nitroprusside significantly reduced force in the treated region (from 10.3 +/- 0.8 to 7.9 +/- 0.9 g) and segment work (from 1889 +/- 296 to 1254 +/- 252 g.mm/min). In the LVH group, regional work, force, and shortening did not change. In the CFX regions of both groups, regional myocardial mechanics, as well as regional myocardial O2 consumption, were not altered during nitroprusside infusion. Cyclic GMP levels were elevated to a much greater extent in the LVH animals (from 3.26 +/- 0.60 to 15.23 +/- 4.65 pmole/g) than in the control animals (from 2.16 +/- 0.60 to 2.89 +/- 0.56 pmole/g). Thus, in contrast to control myocardium, significant increases in cGMP production during nitroprusside infusion failed to produce negative inotropy in LVH. These findings suggest an uncoupling between the second messenger and systems controlling muscle contraction.

Animals↗

PubMed1994

Milrinone, a cyclic AMP-phosphodiesterase inhibitor, has differential effects on regional myocardial work and oxygen consumption in experimental left ventricular hypertrophy.

OBJECTIVE: The aim was to test the hypothesis that local myocardial work and O2 consumption would respond differentially to milrinone, a selective cyclic AMP-phosphodiesterase inhibitor, in left ventricular hypertrophy due to differences in myocardial cyclic AMP-phosphodiesterase activity. METHODS: The effect of milrinone on regional segment work and regional O2 consumption was measured in 12 open chest anaesthetised dogs with left ventricular hypertrophy induced by valvular aortic stenosis and in 10 age matched control dogs. Regional myocardial work was calculated as the integrated product of instantaneous force development (miniature transducer) and segment shortening (sonomicrometer). Regional O2 consumption was calculated from coronary blood flow (radiolabelled microspheres) and O2 saturations in small regional vessels (microspectrophotometry). Low Km phosphodiesterase activity was assayed by measuring the hydrolysis of radiolabelled cyclic AMP. RESULTS: Milrinone increased left ventricular dP/dtmax by approximately 60-70% in both control [2808(SEM 314) to 4584(660) mm Hg.s-1] and left ventricular hypertrophy [3279(258) to 5589(470) mm-Hg.s-1]. Regional work increased significantly in control [612(88) to 955(101) g.mm.min-1], while the increase was not significant in left ventricular hypertrophy [859(139) to 974(172) g.mm.min-1]. Regional O2 consumption increased significantly with milrinone in left ventricular hypertrophy [8.1(1.2) to 13.1(2.4) ml O2.min-1.100 g-1], but the increase was not significant in control [6.9(1.2) to 7.4(1.0) ml O2.min-1.100 g-1]. Myocardial stiffness during ejection was increased by milrinone to a significantly greater extent in animals with left ventricular hypertrophy. These effects were not related to differences in cyclic AMP-phosphodiesterase activity between control hearts and hearts with left ventricular hypertrophy [393(45) v 402(36) pmol.mg protein-1.1]. CONCLUSIONS: Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Effect of dopamine on local segment work and O2 consumption in collateral-dependent myocardium.

To test the hypothesis that dopamine-stimulated work and myocardial O2 consumption (MVO2) in collateral-dependent myocardium would be reduced, Ameroid constrictors were implanted around the circumflex coronary artery (CFX) in nine dogs. Four weeks later, in an anesthetized open-chest preparation, segment length (ultrasonic dimension gauge) and force (miniature force transducer) were measured in myocardium supplied by the CFX and left anterior descending (LAD) coronary arteries. Work in each region was calculated as the systolic area under the force-length curve. Corresponding regional MVO2 was calculated from local O2 extraction (microspectrophotometry) and flow (radiolabeled microspheres). Dopamine infusion (15 micrograms.kg-1.min-1) increased regional work from 262 +/- 56 to 733 +/- 171 mm.g.min-1 in the control (LAD) region, but to a much smaller extent in the collateral-dependent (CFX) region (from 249 +/- 82 to 414 +/- 81 mm.g.min-1). However, regional MVO2 increased to about the same extent in the CFX (from 6.0 +/- 0.7 to 12.4 +/- 0.9 ml O2.min-1 times 100 g-1) and the LAD region (from 7.0 +/- 0.6 to 14.5 +/- 1.3 ml O2.min-1 times 100 g-1). O2 extraction was not elevated in the CFX region. Therefore, the functional impairment was not secondary to O2 supply or consumption limitations.

Animals↗

PubMed1993

Relationship between cyclic-AMP content, regional myocardial function and O2 consumption in experimental left ventricular hypertrophy: effect of negative inotropes.

The aim of this study was to examine the hypothesis that negative inotropic agents that lower myocyte cyclic-AMP by different means would have similar effects on local myocardial segment work and O2 consumption in control hearts, but that this response would differ in left ventricular hypertrophy (LVH) induced by aortic valve stenosis. Open chest anesthesized LVH and control dogs were studied before and during esmolol (100 micrograms/kg/min) and acetylcholine (100 micrograms/kg/min) infusion. Regional work was calculated as the integrated product of instantaneous force (miniature transducer) and shortening (sonomicrometry) per min. Regional O2 consumption was calculated from blood flow (radioactive microspheres) and O2 saturation of small frozen vessels (microspectrophotometry). Cyclic-AMP level was determined with a competitive binding assay using 3H-cyclic-AMP and was found to be 731 +/- 90 (mean +/- S.D.) pmol/g in control and 711 +/- 163 in LVH. There were similar decreases in cyclic-AMP levels in control hearts with acetylcholine (365 +/- 135) and the beta adrenergic blocker (430 +/- 95). In LVH, esmolol lowered cyclic-AMP (383 +/- 39), but acetylcholine did not (689 +/- 105). In control animals, regional O2 consumption (7.7 +/- 0.6, 5.6 +/- 0.4 and 5.6 +/- 0.5 ml O2/min/100 g, control, acetylcholine, esmolol, respectively) and segment work (878 +/- 82, 546 +/- 80, 627 +/- 66 g*mm/min) fell to similar levels with these agents. Similar decreases were found in LVH with esmolol for O2 consumption (7.1 +/- 1.2, 5.1 +/- 1.0, baseline, esmolol) and segment work (895 +/- 140, 427 +/- 65). Acetylcholine had no significant effect on segment work (800 +/- 201), but did lower regional O2 consumption (4.0 +/- 0.7) in LVH dogs. It is concluded that there is a strong relationship between the level of cyclic-AMP and myocardial function and O2 consumption in control hearts. The action of acetylcholine is altered in LVH leading to an uncoupling between regional cyclic-AMP, function and metabolism.

Analysis of Variance↗

PubMed1993

Role of ischemia-reperfusion on myocardial cyclic AMP and cyclic AMP phosphodiesterase: effects of amrinone on regional myocardial force and shortening.

This study tested the hypothesis that a reperfused ischemic myocardial region of the dog heart would be unable to increase its function in response to amrinone, a specific cyclic AMP phosphodiesterase (cAMP-PDE) inhibitor, due to loss of cAMP-PDE activity in the region. The global contractility (+dp/dtmax), regional percent shortening (ultrasonic crystals), and developed force (miniature force gauge) were measured on a continuous basis throughout a 6-hour experiment and regional blood flow (radioactive microspheres) in open-chest pentobarbital-anesthetized mongrel dogs. The left anterior descending coronary artery (LAD) was isolated and ligated for 2 hours and allowed to reperfuse for 4 hours. This myocardial region was compared to a nonischemic region supplied by the circumflex artery. At the end of the 4-hour reperfusion period, 9 dogs were treated with amrinone (5 mg/kg) and three dogs were not treated with amrinone. The hearts were rapidly excised and frozen in liquid nitrogen. Cyclic AMP and cAMP-PDE activity was determined in homogenates of myocardial tissue. Blood flow decreased during occlusion in the LAD region and returned toward control with reperfusion. Flow increased nonsignificantly with amrinone. the basal cyclic AMP content of the two regions was not different. The cAMP-PDE activity was reduced 24% in the LAD region compared to the control region. There were no ischemia-induced changes in the enzyme characteristics. These experiments demonstrated increased global function in the ischemic reperfused myocardium after amrinone was administered (dP/dtmax: 2092 +/- 538 to 3277 +/- 688 mmHg/sec).(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Effect of isoproterenol on regional myocardial segment work, O2 consumption, and oxygen balance.

We tested the hypothesis that positive inotropic stimulation by isoproterenol alters the relationship between regional segment work and regional myocardial oxygen consumption. Regional parameters were compared with external cardiac work and global LV oxygen consumption. In anesthetized open-chest dogs, regional myocardial segment length (ultrasonic dimension crystals) and force development (miniature force transducer) were measured. The integrated multiples of myocardial shortening by corresponding force during an averaged beat expressed segment work (area under the systolic portion of the length-force loop). External cardiac work was calculated from aortic blood pressure and cardiac output. Global and regional myocardial MVO2 were evaluated at baseline and during intravenous infusion of isoproterenol (0.5 and 1.0 micrograms/kg per min). Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry of frozen myocardial biopsies was used to evaluate O2 saturation in small arteries and veins. These parameters were used to calculate regional MVO2. Arterial and coronary sinus O2 saturation was used to calculate global LV O2 consumption. Regional myocardial O2 balance was estimated by measurement of NADH redox level using surface fluorometry. It was found that 0.5 micrograms/kg per min isoproterenol increased regional segment work/minute from 4650 +/- 495 to 6750 +/- 750 mm.g/min. Corresponding regional oxygen consumption was disproportionately increased from 5.43 +/- 0.61 to 15.24 +/- 1.37 ml/min per 100 g. External cardiac work was found to decrease from 728 +/- 13 to 562 +/- 25 mmHg.1/min (due to decreased aortic blood pressure), whereas global myocardial O2 consumption increased. Regional myocardial O2 extraction and NADH fluorescence were elevated, indicating impaired tissue oxygenation. Regional MVO2 was increased by 153 +/- 56%, but regional work by only 45.3 +/- 33% (P < 0.05). These results indicate that regional contraction efficiency was markedly reduced by isoproterenol.

Animals↗

PubMed1991

Relationship between adenylate cyclase activity and regional myocardial energetics in experimental left ventricular hypertrophy.

The aim of this study was to examine the responsiveness of the hypertrophied left ventricle to beta-adrenergic stimulation in a pressure overload model produced by valvular aortic stenosis and characterized by reduced beta-adrenoceptor number. The study was designed to correlate changes in global and regional cardiac work and energetics in response to isoproterenol with adenylate cyclase activity. Eleven anesthetized dogs with left ventricular hypertrophy and 11 controls were studied at rest and during 0.5 and 1.0 micrograms/kg/min isoproterenol infusion. We measured regional work from segment length and force changes with ultrasonic dimension crystals and miniature force gauges in addition to arterial and left ventricular blood pressure and cardiac output. Regional myocardial oxygen consumption was calculated from O2 extraction using microspectrophotometry and blood flow using radioactively labeled microspheres. Adenylate cyclase activity was assayed at baseline and after stimulation with forskolin. Isoproterenol significantly increased heart rate, dP/dtmax, cardiac output, and external work to similar levels in control and hypertrophied animals. Similarly, regional work increased from 463 +/- 115 to 995 +/- 584 g x mm/min for controls and from 392 +/- 156 to 1175 +/- 577 for hypertrophied dogs with high dose isoproterenol. Regional O2 consumption also increased to similar levels (20.3 +/- 14.7 vs 16.2 +/- 6.3 ml O2/min/100 g) in both groups. Adenylate cyclase activity was lower in hypertrophy at baseline (23.9 +/- 7.3 vs 62.9 +/- 14.2 pM/min/mg protein for controls), but was the same as for controls with forskolin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1991

Augmented efficiency of regional myocardial work by ouabain.

STUDY OBJECTIVE: The effect of ouabain on regional myocardial mechanics and corresponding regional myocardial oxygen consumption was investigated. DESIGN: Regional myocardial segment length (ultrasonic dimension crystals) and force development (miniature strain gauge) were measured. The integrated multiples of myocardial shortening by corresponding force during an averaged beat was used to express regional segment work (= area under the systolic portion of the length-force loop). External cardiac work was calculated from aortic blood pressure and cardiac output. Global and regional myocardial O2 consumption (MVO2) were evaluated at baseline and during intravenous infusion of ouabain (7 micrograms.kg-1.min-1). Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry of frozen myocardial biopsies was used to evaluate O2 saturation in small arteries and veins. These variables were used to calculate regional myocardial MVO2. Arterial and coronary sinus O2 saturation was used to calculate global left ventricular O2 consumption. Myocardial efficiency was expressed as regional work/regional myocardial MVO2. SUBJECTS: Ten open chest anaesthetised dogs, weight about 20 kg, were used. MEASUREMENTS AND MAIN RESULTS: Ouabain increased regional myocardial segment work [from 5291(SEM 1067) to 8916(2338) mm.g-1.min-1] to a greater extent than regional myocardial MVO2 [from 6.33(0.75) to 8.54(0.75) ml O2.min-1.100 g-1]. Regional efficiency was increased from 734(78) to 1036(160) g.mm.ml O2(-1).100 g-1. External efficiency was not raised. Percent shortening was increased to a greater extent than peak force development (+76% v + 38%), possibly indicating increased myocardial compliance. The length-force loop was shifted upward and to the right. CONCLUSIONS: Ouabain increases regional efficiency of myocardial contraction.

Animals↗

PubMed1990

Alterations in the regional beta adrenergic system in experimental left ventricular hypertrophy.

STUDY OBJECTIVE - The aim of the study was to determine the changes in the beta adrenergic system induced by cardiac hypertrophy due to valvular aortic stenosis. DESIGN - Density of beta adrenoceptors, cardiac tissue noradrenalime concentrations, coronary blood flow (using radioactive microspheres), and haemodynamic variables were compared in a model of experimental aortic valve stenosis of 6 month's duration and in sham operated controls. SUBJECTS - 14 mongrel dogs with aortic stenosis and eight sham operated litter mates were used in the studies. MEASUREMENTS and RESULTS - Heart weight to body weight ratio was 33% greater in dogs with aortic valve stenosis than in controls. There were no haemodynamic differences except for a left ventricular to aortic systolic pressure gradient of 38 (SD 22) mm Hg in the aortic stenosis group. Response of left ventricular dP/dtmax to dopamine was similar in the two groups, as was coronary flow. Density of beta adrenoceptors (Bmax) as measured by (125I)-iodopindolol binding was reduced in ventricles from the aortic stenosis group compared to control: 41.2(13.3) v 59.1(8.1) fmol.mg-1 protein, p less than 0.005. Affinity of receptor for ligand (Kd) was not affected by cardiac hypertrophy. Tissue noradrenaline concentration was reduced in the hypertrophy group: 1108(402) (control) v 438(13) ng.g-1 initial wet weight (aortic stenosis), p less than 0.05. There were no significant subepicardial v subendocardial differences in any variable. CONCLUSIONS - Cardiac hypertrophy induced by aortic valve stenosis over a 6 month period is accompanied by a decrease in the density of ventricular beta adrenoceptors per gram and a decrease in ventricular noradrenaline concentration, though responsiveness of the whole heart is maintained.

Animals↗

PubMed1990

Effect of hyper- and hypovolaemia on regional myocardial oxygen consumption.

STUDY OBJECTIVE - The purpose of the investigation was to study the effect of preload on coronary blood flow and myocardial oxygen consumption in subendocardial and subepicardial regions of left ventricular free wall. DESIGN - Ventricular volume in anaesthetised open chest dogs was altered over a range of 20% to produce hypovolaemia (10-15% exsanguination) or hypervolaemia (colloid infusion), allowing measurements of regional blood flow and oxygen consumption with varying preloads. beta Adrenergic blockade was used to limit changes in inotropy, and heart rate was kept constant by pacing at 150 beats.min-1. SUBJECTS - 9 mongrel dogs of either sex weighing 24.9 (SEM 4.1) kg were studied. MEASUREMENTS and RESULTS - Left ventricular volume was calculated from ultrasonic measurements of long and short axis end diastolic diameters and wall thickness. Regional myocardial blood flow was estimated using radioactive microspheres, and oxygen consumption in each region was determined from microspectrophotometric measurements of oxygen saturations in small arteries and veins. Hypervolaemia increased subepicardial blood flow from 66.8(6.9) (normovolaemic) to 114.1(13.5) ml.min-1.100 g-1, and regional oxygen consumption from 4.08(0.57) to 6.44(1.08) ml.min-1.100 g-1. Values in the subendocardium were similar, except for oxygen consumption, which increased less than in the subepicardium. Left ventricular end diastolic volume, pressure, and output were each increased in hypervolaemia, but not dP/dt and systolic aortic pressure. Hypovolaemia reduced blood pressures without reducing end diastolic volume. CONCLUSIONS - Augmented flow work produced by increased preload (even in the absence of changes in pressure work) increases myocardial oxygen supply equally in the subepicardium and the subendocardium, while oxygen extraction and consumption are preferentially augmented in the subepicardium.

Animals↗