Biomedical subjects

H R Weiss

Publications and source records attributed to H R Weiss.

At least 91 records · Page 5Linked to original sources

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

Effect of hypoxic and carbon monoxide-induced hypoxia on regional myocardial segment work and O2 consumption.

The purpose of this study was to investigate the potentially greater responses of regional myocardial work and O2 consumption to hypoxic hypoxia than to CO-induced hypoxia. Twenty open-chest anesthetized dogs were studied under control and four hypoxic conditions, hypoxic hypoxia induced with either 8% O2 (SaO2 = 56%) or 6% O2 (SaO2 = 40%) gas mixtures, or CO-induced hypoxia produced by a 1% CO gas mixture for either 7 min (SaO2 = 67%; SaCO = 30%) or 20 min (SaO2 = 40%; SaCO = 56%). Ultrasonic crystals and a force gauge were utilized to measure myocardial shortening and force. Regional myocardial segment work was calculated by integrating myocardial segment shortening multiplied by its corresponding force. Radioactive microspheres were used to measure regional coronary blood flow during each condition. Transmural biopsies were utilized to measure arterial and venous O2 saturation with a four-wavelength microspectrophotometric method. Regional O2 extraction and consumption were calculated. Regional coronary blood flow (77 +/- 38 ml/min per 100 g, control) increased with severe hypoxic hypoxia (293 +/- 206) and CO-induced hypoxia (150 +/- 128). Regional myocardial O2 extraction was decreased with both hypoxic and CO hypoxia. Regional myocardial O2 consumption was maintained even with severe hypoxic and CO hypoxia. Regional myocardial segment work/min increased from 343 +/- 205 g* mm/min with increasing levels of hypoxic hypoxia (564 +/- 677) and decreased with increasing levels of CO hypoxia (169 +/- 111). Regional segment work increased with increasing levels of hypoxic hypoxia and decreased with increasing CO hypoxia. The differential effects on segment work caused by the two types of hypoxia may be due to direct metabolic or autonomic differences.

Animals↗

PubMed1994

Effects of topical methylene blue on cyclic GMP level, blood flow, and O2 consumption in focal cerebral ischaemia.

We hypothesized that a decrease in cyclic GMP, a second messenger in the glutamate-nitric oxide pathway, would reduce oxygen consumption and improve O2 balance in the ischaemic cerebral cortex. To test this hypothesis, a study was performed in unilateral middle cerebral artery occluded rats which were assigned to either a control or methylene blue (10(-3) M) group. Regional cerebral blood flow was determined using 14C-iodoantipyrine and regional arterial and venous O2 saturations were determined by microspectrophotometry (n = 6). Cyclic GMP level was measured by radioimmunoassay (n = 8). Guanylate cyclase and cyclic GMP-phosphodiesterase activities were determined in an additional set of control rats (n = 10). The cyclic GMP levels were not different between the ischaemic and contralateral areas in the control group. Compared to the cyclic GMP in the control ischaemic cortex, topical methylene blue significantly decreased the cyclic GMP level by 56% in the ischaemic cortex of the methylene blue group. Ischaemia did not alter the activities of guanylate cyclase but mildly decreased cyclic GMP-phosphodiesterase. The regional cerebral blood flow and O2 consumption in the control group were 50% and 32% lower than those in corresponding contralateral cortex. Topical methylene blue did not alter regional cerebral blood flow and O2 consumption in the ischaemic cortex. Our data showed that cyclic GMP is not a major controller on O2 supply or O2 consumption in the ischaemic brain.

3',5'-Cyclic-GMP Phosphodiesterases↗

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 increased myocardial cyclic GMP induced by cyclic GMP-phosphodiesterase inhibition on oxygen consumption and supply of rabbit hearts.

1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor. 2. The study was conducted in three groups (vehicle, 10(-3) and 3 x 10(-3) mol/L zaprinast) of anaesthetized open-chest New Zealand white rabbits (n = 24). Coronary blood flow (radioactive microspheres), arterial and venous O2 saturation (microspectrophotometry), O2 consumption, cyclic GMP content (competitive binding) and cyclic GMP-phosphodiesterase activity (conversion of 3H-cyclic GMP to 3H-GMP) were determined. 3. Agents were applied to a patch on the myocardial surface and did not cause significant haemodynamic changes, except for bradycardia in the vehicle and low dose group. 4. The total myocardial cyclic GMP-phosphodiesterase activity was 148 +/- 14 while the zaprinast (10 mumol/L) inhibitable activity averaged 63 +/- 8 pmol/mg protein per min. Cyclic GMP content was increased with increasing doses of zaprinast (vehicle, 4.308 +/- 0.349 pmol/g; low dose zaprinast, 4.803 +/- 0.279 and high dose zaprinast, 7.938 +/- 1.304 pmol/g). 5. Coronary blood flow was not different after treatment (198 +/- 11, 209 +/- 10 and 153 +/- 9 mL/min per 100 g for the vehicle, low and high dose zaprinast, respectively). 6. Under control conditions, 48% of the small veins had O2 saturations below 50%. With zaprinast, this value was reduced to 19% for the low and 24% for the high dose. 7. Average venous O2 saturation increased with zaprinast (49 +/- 2%, 61 +/- 3% and 59 +/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP 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↗

PubMed1994

Effect of isoproterenol on the relationship between regional cyclic AMP and local coronary blood flow in the canine myocardium.

This study was designed to test in the dog heart the hypothesis that local levels of myocardial cyclic AMP (cAMP) would exhibit significant heterogeneity; that this heterogeneity would correlate with local coronary blood flow, and that this association would be increased with isoproterenol stimulation. Anesthetized open-chest dogs were studied during control (n = 7) or isoproterenol (0.5 micrograms/kg/min) infusion (n = 7) to test this hypothesis. Coronary blood flow was measured with radioactive microspheres, and cAMP was determined with a competitive binding assay using 3H-cAMP. Significant heterogeneity in cAMP existed during basal [592 pmol/g, within-animal coefficient of variation (100 x mean/SD) = 45.2%] and isoproterenol stimulated [872 (27.3%)] conditions. Method variability could account for only 28% of the total basal variability. No correlation between local blood flow [87 ml/min/100 g (12.9%)] and local cAMP was found under control conditions. Both coronary blood flow [206 (20.8%)] and cAMP levels increased significantly with isoproterenol stimulation. There was a significant correlation between normalized stimulated blood flow and cAMP: % flow = 0.39 (% cAMP) + 61.3 (r = 0.48, p < 0.0001). We conclude that significant heterogeneity in myocardial cAMP levels exists, and that this heterogeneity correlates with coronary blood flow heterogeneity during isoproterenol stimulation.

Animals↗

PubMed1994

Effects of inhibition of nitric oxide synthase on blood-brain barrier transport in focal cerebral ischemia.

This study was performed to determine whether nitric oxide (NO) alters the transport of small hydrophilic molecules across the blood-brain barrier in focal cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and by measuring the blood-brain barrier transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB) in the rats with middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the mean arterial blood pressure from 91 +/- 9 to 134 +/- 13 mm Hg. The Ki of the ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO) in the control animals without the L-NAME treatment. However, in the L-NAME-treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in the L-NAME group was significantly lower (-54%) than that of the control group. L-NAME did not affect Ki significantly in the nonischemic brain regions. Our data demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly decreased the Ki in the focal ischemic area of the brain without causing significant changes in the nonischemic tissue. Our results suggest that NO may participate in increasing transport of small hydrophilic molecules across the blood-brain barrier in focal ischemia.

Amino Acid Oxidoreductases↗

PubMed1994

Nitric oxide synthase inhibition alters cerebral blood flow and oxygen balance in focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: This study investigated whether the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) would alter blood flow and oxygen balance in the ischemic cerebrocortex of isoflurane-anesthetized Long-Evans rats. METHODS: Fifteen minutes after middle cerebral artery occlusion, L-NAME (1.5 mg/min per kilogram) was infused intravenously to the L-NAME group (n = 14), and normal saline was given to the control group (n = 14) for 45 minutes. In each group, regional cerebral blood flow was determined with [14C]iodoantipyrine, and arterial and venous oxygen saturations were determined by microspectrophotometry. RESULTS: In both groups regional cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex ([mean +/- SD] 55 +/- 13 versus 110 +/- 29 mL/min per 100 g in the control group and 35 +/- 13 versus 90 +/- 24 mL/min per 100 g in the L-NAME group). Compared with the blood flow in the ischemic cortex of the control group, L-NAME significantly reduced ischemic blood flow by 36%. Venous oxygen saturation was significantly increased in the ischemic cortex (41 +/- 1% versus 44 +/- 3%) but decreased in the contralateral cortex (65 +/- 3% versus 61 +/- 4%) by L-NAME. Calculated ischemic cortical oxygen consumption in the L-NAME group was 39% lower than that in the corresponding control group, whereas the difference was only 11% in the contralateral sides between groups. In both groups, the ratio of oxygen supply to consumption was lower in the ischemic than in the nonischemic regions. In the ischemic cortex, this ratio was significantly lower in the control group than in the L-NAME group (1.7 +/- 0.1 versus 1.9 +/- 0.1). In contrast, the ratio tended to be decreased by L-NAME in nonischemic regions. CONCLUSIONS: These observations suggest that despite a decrease in cerebral blood flow, inhibition of nitric oxide synthesis mildly improves the oxygen supply and consumption balance in the ischemic cortex.

Amino Acid Oxidoreductases↗

PubMed1994

Effect of ketamine on heterogeneity of cerebral microregional venous O2 saturation in the rat.

Heterogeneity of microregional O2 supply and consumption balance exists in the brain. Previous studies have shown that anesthetics such as pentobarbital and isoflurane, decrease the heterogeneity of O2 saturation in the small veins of the brain. This study was performed to determine whether ketamine, an anesthetic, would alter this heterogeneity. Rats were anesthetized with isoflurane for the cannulation of the femoral artery and vein. Ninety minutes after discontinuation of isoflurane, they either received injections with ketamine 100 mg/kg intraperitoneally (IP) (n = 7) or were used as conscious controls (n = 7). In each rat, regional cerebral blood flow (rCBF) was determined by 14C-iodoantipyrine autoradiography, and microregional arterial and venous (diameter 20-100 microns) O2 saturation was measured by microspectrophotometry in the anterior cortex, posterior cortex, and pons. The average rCBF and O2 consumption were similar between the two groups in each brain region except in the anterior cortex, where the O2 consumption of the ketamine group was slightly higher than that of the conscious animals. The average regional O2 supply-to-consumption ratios were similar in the three brain regions in both of the groups. However, there was heterogeneity of the O2 saturation in small veins in all the brain regions that we studied. The coefficient of variation [CV = (SD/mean X 100] of venous O2 saturation of the ketamine group in the anterior cortex (19.8 +/- 7.2), in the posterior cortex (18.8 +/- 9.4), and in the pons (16.7 +/- 6.5) was not significantly different from that in the conscious animals (22.8 +/- 6.4, 23.1 +/- 5.3, and 15.7 +/- 6.4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[Effects of Schroth's rehabilitation program on the self concept of scoliosis patients].

A total of 37 scoliotic patients (33 female, 4 male), aged 20-57 years, participated in a pre-/post-interview study on the basis of the Frankfurt self-concept scales FSKN (Frankfurter Selbstkonzeptskalen; Deusinger 1986). The patients stayed at the Katharina Schroth Clinic for 4 to 6 weeks, with questionnaires to be filled in 1-2 days after admission (pre-interviewing) and 2 days before discharge (post-interviewing). The study findings indicated a positive impact of the in-patient treatment relative to a variety of patient self-concepts. This is clearly suggested by the self-ratings concerning: general coping ability; own sensitivity and mood; own self-assertion towards groups and significant others; perceived appreciation by others; feelings towards and relationship with others; general self-worth; and own ability to make contact and interact. The statistically significant changes in a positive direction found for 7 of 10 self-concept scales, are interpreted to the effect that the in-patient treatment on the whole has ushered in a process of emotional stabilization in the patients, which certainly would be considered an essential precondition for their continued capacity for work.

Adaptation, Psychological↗

PubMed1993

Diminished effect of inhibition of nitric oxide synthase on regional cerebral vascular resistance in conscious and in isoflurane anesthetized rats during hemorrhage.

Effects of a nitric oxide (NO) synthase inhibitor on regional cerebral vascular resistance (rCVR) and regional cerebral blood flow (rCBF) were studied during a severe hemorrhage in conscious and in isoflurane anesthetized groups of rats. Half of each group was infused with NG-nitro-L-arginine-methyl ester (L-NAME), a NO synthase inhibitor, at a rate of 2 mg.kg-1.min-1 for 30 min. Half of the L-NAME infused and half of the normal saline infused rats were bled to reduce the mean arterial blood pressure (MAP) to 44-49 mmHg. rCBF was measured using [14C]iodoantipyrine. rCVR was calculated as the ratio of MAP to rCBF. In the conscious non-hemorrhagic rats, L-NAME markedly increased rCVR in all the brain regions that we studied. In the conscious rats without L-NAME treatment, hemorrhage decreased rCVR in most of the brain regions. With L-NAME treatment in this group, hemorrhage increased rCVR only in the rostral part of the brain. Isoflurane decreased rCVR in most of the brain regions except the cortical area. L-NAME markedly increased rCVR in all the brain regions that we studied in the isoflurane anesthetized rats. In the isoflurane anesthetized rats, hemorrhage did not reduce rCVR in any of the brain regions. In the isoflurane anesthetized hemorrhagic rats, L-NAME did not significantly affect rCVR in any of the brain regions that we studied. We found that L-NAME increased rCVR to a greater extent in the non-hemorrhagic rats than in the hemorrhagic rats in both the conscious and in the isoflurane anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1993

Effect of isoproterenol on coronary blood flow and signal transduction responses in thyroxine-treated rabbit hearts.

This study examined the hypothesis that treatment with thyroxine (T4) would alter the coronary blood flow and signal transduction responses of the rabbit heart. T4 was administered for 16 days by subcutaneous time-release pellets (3 mg/kg/day) in 3 kg New Zealand white rabbits. Four groups of anesthetized open-chest rabbits (control, control+isoproterenol (ISO, 0.5 microgram/kg/min for 15 min), T4, and T4 + ISO) were used to determine coronary blood flow (radioactive microspheres), cyclic AMP content (competitive binding), low Km cyclic-AMP-phosphodiesterase activity (cyclic AMP-PDE, conversion of 3H-cyclic AMP to 3H-AMP) and beta-adrenoceptor number and affinity (125I-iodocyano-pindolol). Coronary blood flow was increased from control by ISO from 167 +/- 59 to 354 +/- 157 ml/min/100 g. T4 did not cause cardiac hypertrophy, but increased baseline coronary blood flow to 269 +/- 115 ml/min/100 g. The ISO response was attenuated in terms of blood flow (448 +/- 118) and heart rate with T4. Beta-adrenoceptor numbers increased significantly from 65.7 +/- 9.2 to 81.9 +/- 4.4 fmol/mg protein, while neither soluble (126 +/- 39 vs 119 +/- 15 pmol/mg protein/min) nor particulate cyclic AMP-PDE activity were different between control and T4 animals. Cyclic AMP content was increased from control by both ISO (779 +/- 239 to 1371 +/- 672 pmol/g) and T4 (1143 +/- 244). T4 animals showed a smaller increase in cyclic AMP following ISO (1391 +/- 261). There was not a significant difference between the control and T4 group cyclic AMP level following ISO. Thus, despite increased beta-adrenoceptor numbers, there was a diminished responsiveness of heart rate, coronary blood flow and cyclic AMP levels to isoproterenol in the T4-treated rabbit hearts.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1993

Capillary perfusion in the occluded-reperfused canine myocardium: evidence for slowed reflow.

The purpose of this study was to determine if the no-reflow phenomenon in the occluded/reperfused dog heart was anatomical (capillary bed could not be perfused) or functional (slowed capillary perfusion). The left anterior descending (LAD) coronary artery was isolated in anesthetized open-chest dogs. The LAD was occluded (2 hr) then reperfused (4 hr). A total of 14 dogs were assigned to one of two groups: The multiple pass (MP) or single pass (SP) group. Fluorescent labeled dextran (FITC) was injected and circulated either for 10 min in the MP group or for one pass of the circulation in the SP group. In the last 2 min, the MP group was asphyxiated. Hearts were excised and frozen in liquid nitrogen. The LAD and control region were isolated and frozen sections (5 microns) obtained. Sections were photographed under fluorescent light and then immunohistochemically stained. The microvessels were identified by visualizing the endothelium with a Factor VIII antibody. The specific areas photographed were relocated. The total number of capillaries, determined by stain outlining a lumen of no greater than 10 microns in diameter, were counted. This number was compared to the number of microvessels containing FITC-dextran. There was no difference in the total perfusable capillary bed in the MP group between the control and LAD regions (80 +/- 4 and 82 +/- 10%). In the SP group, there was a significant difference between the control and LAD regions (59 +/- 25 and 46 +/- 14%). The percentage of the capillary bed perfused in the SP group was less than the MP group in each region. Closest individual analysis of the perfused capillary distribution in the SP group, showed the distribution in the LAD region was random, potentially clustered and more dispersed compared to the control region. This study provides data against physical obstruction of the capillary bed secondary to ischemia. The data suggest sluggish and clustered perfusion in the occluded-reperfused myocardium during a single pass of the coronary circulation.

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

Imbalance of regional cerebral blood flow and oxygen consumption: effect of vascular alpha adrenoceptor blockade.

This study tested the hypothesis that local cerebral O2 supply and consumption are not precisely balanced and that vascular alpha adrenoceptors affect this equilibrium. Twenty-two male Long-Evans rats were used in this study. Cerebral blood flow was determined in six regions, using 4-iodo [N-methyl-14C]antipyrine. Oxygen saturation was determined microspectrophotometrically in small veins draining three regions of the brain of the rat. Comparisons were made between a control group and a group given N-methyl chlorpromazine, an alpha adrenergic blocker that does not affect central neuronal alpha adrenoceptors. Under control conditions, no regional differences in flow were found. With N-methyl chlorpromazine, cerebral blood flow in the basal ganglia was greater than all other regions, except the frontal cortex. Cerebral O2 consumption was higher in the frontal cortex than the medulla under control conditions and this difference was not statistically significant after N-methyl chlorpromazine. Cerebral venous O2 saturations (a measure of cerebral O2 supply/consumption balance) were found to be significantly heterogeneous under control conditions. The coefficient of variation (CV = 100 x SD/mean) averaged 18%. The average cerebral venous O2 saturation was 59 +/- 11%. Administration of N-methyl chlorpromazine significantly reduced this heterogeneity through a reduction in the number of veins with low O2 saturations (CV = 11%). The average value increased slightly but significantly to 62 +/- 8%. Thus, N-methyl chlorpromazine eliminated many microregions of high O2 extraction. This indicated that vascular alpha adrenoceptors limit cerebral blood flow to some of the brain regions.

Adrenergic alpha-Antagonists↗

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↗