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H R Weiss

Publications and source records attributed to H R Weiss.

At least 109 records · Page 6Linked to original sources

Effect of cervical sympathectomy and hypoxia on the heterogeneity of O2 saturation of small cerebrocortical veins.

This study evaluated the hypothesis that the sympathetic nervous system was one of the factors increasing the heterogeneity of cerebrocortical venous O2 saturation and this heterogeneity would be greater during hypoxia when cervical sympathetic activity was elevated. Thirty-two male Long-Evans rats were either sham operated (n = 16) or received bilateral cervical sympathectomy (n = 16). One-half of the animals (n = 8) in each treatment were challenged by hypoxia (8% O2 in N2). Cerebral blood flow was determined in five brain regions with [14C]iodoantipyrine. Oxygen saturation was measured microspectrophotometrically in small cerebrocortical arteries and veins. The degree of hypoxic hyperemia was not significantly different between sham-operated and sympathectomized rats. Cortical venous O2 saturations, indicating the balance between O2 supply and consumption, were significantly more heterogeneous in the sham-operated group under both normoxic and hypoxic conditions. The coefficient of variation (CV = 100 x SD/mean) for the normoxic sham-operated animals was 24.9% and the average venous O2 saturation was 53.8%. During hypoxia, venous O2 saturation was significantly decreased to 43.1% without a change in CV (24.5%). Sympathectomy significantly reduced this heterogeneity through a reduction in the number of low O2 saturation veins (CV = 13.2%) under normoxic conditions and the effect was similar under hypoxic conditions (CV = 15.3%). In both sham-operated and sympathectomized groups, hypoxia elicited a significantly higher cerebrocortical O2 consumption. Thus, bilateral cervical sympathectomy improved the O2 supply in selective cerebrocortical regions with high O2 extraction. However, the effect of sympathetic innervation on the heterogeneity of cerebrocortical venous O2 saturation was not potentiated by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Middle cerebral artery occlusion increases cerebral capillary permeability.

One hour after middle cerebral artery occlusion, the regional blood to brain transfer coefficient of alpha-aminoisobutyric acid was determined in eight barbiturate anaesthetized rats. The transfer coefficient (microliter/min-1/g-1) was significantly higher in the ischaemic cortex (10.6 +/- 2.3) than in the contralateral cortex (6.5 +/- 1.0). Cerebral regional capillary surface area was determined in another group of twelve rats using an alkaline phosphatase stain for the total capillary bed and fluorescein isothiocyanate-dextran to visualize the perfused capillaries. Perfused capillary surface area (cm2/cm3) was lower in the ischaemic cortex (141 +/- 31) than in the contralateral cortex (426 +/- 32). Using these values for the transfer coefficient, surface area and our previously published data of regional cerebral blood flow after middle cerebral artery occlusion, we calculated the extraction fraction of alpha-aminoisobutyric acid, the permeability-surface area product and the permeability of cerebral regional capillary beds. Although, there are numerous reports of permeability-surface area product of brain capillaries, to our knowledge, the permeability has never been determined before. The calculated extraction fraction ratio for alpha-aminoisobutyric acid for ischaemic cortex/contralateral cortex was 3.1. Similar ratios for permeability-surface area product and capillary permeability were 1.6 and 4.4, respectively. Thus, there was a more than four fold increase in capillary permeability to small molecules in the ischaemic cortex one hour after middle cerebral artery occlusion.

Aminoisobutyric Acids↗

Effects of pentobarbital and isoflurane on regional cerebral oxygen extraction and consumption with middle cerebral artery occlusion in rats.

BACKGROUND: When compared with barbiturates, isoflurane may lack protective effects during focal cerebral ischemia. The reason for this difference is not clear. In this study, regional cerebral blood flow (rCBF), arterial and venous O2 saturation, and O2 extraction were compared in the ischemic cortex and in the nonischemic brain regions of rats anesthetized with isoflurane or pentobarbital using a microspectrophotometric technique that directly measures the O2 saturation of blood in the small arteries and veins. METHODS: Twenty-eight rats were anesthetized with 1.4% isoflurane or 50 mg/kg pentobarbital. One hour after a middle cerebral artery (MCA) occlusion, rCBF was measured in the ischemic cortex and in the nonischemic brain regions using 14C-iodoantipyrine in one-half of each group of animals. Regional arterial and venous O2 saturation were determined using microspectrophotometry in the other one-half of each group. RESULTS: The rCBF of the ischemic cortex (IC) and the non-ischemic contralateral cortex (CC) of the isoflurane group were significantly higher than those of the pentobarbital group. The venous O2 saturation was significantly less, and the O2 extraction was significantly higher, in the IC than in the nonischemic regions in both groups of animals (pentobarbital group, IC 10.5 +/- 1.1 ml O2.100 ml blood-1, CC 6.3 +/- 0.7; isoflurane group, IC 10.8 +/- 0.6, CC 5.9 +/- 0.2). There was no significant difference between the two groups. CONCLUSIONS: Because the rCBF was less and the O2 extraction was similar, O2 consumption in the focal ischemic area of the brain during pentobarbital anesthesia must have been less than that during isoflurane anesthesia.

Animals↗

Relationship between local myocardial adenylyl cyclase activity and local coronary blood flow in the dog heart.

1. This study tested the hypothesis that heterogeneity of myocardial adenylyl cyclase activity exists and contributes to the heterogeneity of blood flow in canine myocardium, in which flow varies in different areas at any one moment or in a single area at different times. 2. Tissue adenylyl cyclase activity was measured simultaneously with coronary blood flow in the left ventricle of eight anaesthetized open-chest dogs. Coronary flow was measured using radioactive microspheres under control conditions and after sympathetic stimulation. The ventricle was cut into 15 subepicardial and 15 subendocardial sections in which both flow and adenylyl cyclase (basal and forskolin-stimulated) activity were assayed. 3. Control coronary flow was 73.1 +/- 19.9 ml min-1 100 g-1 and ansa subclavia nerve stimulation increased flow to 93.2 +/- 26.1. Baseline adenylyl cyclase activity averaged 51.9 +/- 38.8 pmol min-1 mg protein-1, while forskolin-stimulated activity was 588.2 +/- 393.6. Method variability was approximately 10% of the mean, much less than the biological variability of 70%. 4. Regression analysis of control flow vs baseline adenylyl cyclase activity produced the equation: flow = 0.25 (Adenylyl Cyclase)+60.6, (r = 0.47, P < 0.0001). The equation for stimulated flow vs stimulated adenylyl cyclase was: flow = 0.03 (Adenylyl Cyclase)+73.1, (r = 0.51, P < 0.0001). 5. Thus, significant heterogeneity of tissue adenylyl cyclase activity existed in the heart. There was also a direct linear relationship between adenylyl cyclase activity and coronary flow heterogeneity in canine left ventricle.

Adenylyl Cyclases↗

Cervical sympathectomy reduces the heterogeneity of oxygen saturation in small cerebrocortical veins.

This study evaluated the hypothesis that the peripheral sympathetic nervous system is one of the factors increasing the heterogeneity of venous O2 saturation in selective brain regions. Regional cerebral blood flow and O2 saturation were determined in the anterior cortex, posterior cortex, and medulla of either sham-operated or bilaterally sympathectomized Long-Evans rats. Cerebral venous O2 saturations, indicating the balance between local O2 supply and consumption, were found to be significantly more heterogeneous in the sham-operated group. In the anterior cortex, the coefficient of variation [100(SD/mean)] for the sham-operated animals was 22.4%. Sympathectomy significantly reduced this heterogeneity in the anterior cortex through a reduction in the number of low O2 saturation veins (coefficient of variation 11.7%). Blood flow and O2 consumption in the anterior cortex were not different between groups. The effects of sympathectomy in the posterior cortex were similar to those in the anterior cortex. However, sympathectomy did not alter any measured variables in the medulla. Thus, bilateral superior cervical ganglionectomy reduced the heterogeneity of cerebrocortical venous O2 saturation by reducing the number of low O2 saturation veins in the rostral part of the brain.

Animals↗

Effects of nitric oxide synthase inhibition on regional cerebral blood flow and vascular resistance in conscious and isoflurane-anesthetized rats.

Nitric oxide is an important regulator of the regional cerebral vascular tone. We compared the magnitude of nitric oxide-related changes in the vascular tone by studying the regional cerebral blood flow (rCBF) and vascular resistance in conscious and isoflurane-anesthetized rats by using a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). In the conscious group (n = 12), after cannulation of a femoral artery and two veins under isoflurane anesthesia, rats were allowed to remain awake for 90 min. In the anesthetized group (n = 18), rats were anesthetized with 2% isoflurane and mechanically ventilated. Six rats in each group were treated with L-NAME (2 mg.kg-1 x min-1 for 30 min) or saline. For the remaining rats in the isoflurane-anesthetized group (n = 6), arterial blood pressure was increased by phenylephrine infusion to the same level as that in the L-NAME-treated, isoflurane-anesthetized rats. Regional vascular resistance was determined by the ratio of mean arterial blood pressure and rCBF which was measured by [14C]iodoantipyrine. L-NAME significantly increased mean arterial blood pressure in both the conscious (123 to 158 mm Hg) and anesthetized (82 to 144 mm Hg) rats. Regional vascular resistance increased significantly in all 12 brain regions studied with the average value increasing from 1.19 +/- 0.33 mm Hg.mL-1 x min x 100 g to 2.22 +/- 0.48 (P < 0.0001) in the conscious and from 0.78 +/- 0.27 to 1.61 +/- 0.48 (P < 0.0001) in the isoflurane-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Effect of flow reduction on coronary blood flow heterogeneity.

The purpose of this study was to test the hypothesis that under reduced flow conditions, spatial heterogeneity (segment-to-segment variability) of myocardial blood flow would be inversely proportional to the rate of perfusion and that vasoconstriction would alter this relationship in anesthetized open-chest dogs. A carotid-left circumflex coronary artery shunt was created. Coronary blood flow determinations employed the radioactive microsphere technique. Fifty tissue samples were obtained from the affected left ventricle, including subepicardial and subendocardial samples. The coefficient of variation (CV = 100 x SD/mean), an index of spatial heterogeneity, was computed. Flows were obtained under three separate conditions: control, a 50% flow reduction in the circumflex artery, and vasopressin infusion, in which the administered dose reduced circumflex artery flow by 50%. The within-animal CV increased from a control of 18 +/- 9 to 45 +/- 25 with partial occlusion and 46 +/- 18 with vasopressin. No significant differences in CV were found between the two reduced flow conditions. A significant linear relationship between CV and mean coronary flow was found (r = 0.51, P < 0.001) over the entire range of flows studied (CV = -0.34*flow + 50.91) for control, 50% occlusion, and vasopressin treatment. The correlation was significantly improved (r = 0.69) using the equation CV = (1319.06/flow) + 4.44. Thus, the relative heterogeneity of coronary blood flow increased with reductions in coronary blood flow, regardless of the means of flow reduction.

Analysis of Variance↗

Effect of pentobarbital on cerebral regional venous O2 saturation heterogeneity.

Observed venous O2 saturation inhomogeneity in the brain implies a microregional imbalance in O2 supply/consumption. We hypothesized that this heterogeneity should be decreased by pentobarbital anesthesia through a reduction in regional metabolic heterogeneity. Male, Long-Evans, approximately 350 g rats were either anesthetized with 50 mg/kg pentobarbital (n = 10) or used as a conscious control group (n = 10, catheters inserted two hours earlier under ether anesthesia). In each rat, regional cerebral blood flow was determined by [14C]iodoantipyrine and regional arterial and venous O2 saturation were determined by microspectrophotometry. In the PB group, the mean blood pressure (107 +/- 7 Torr), heart rate (362 +/- 29/min), average cerebral blood flow (63 +/- 19 ml/min/100 g), and average cerebral O2 consumption (3.7 +/- 1.2 ml O2/min/100 g) were lower than those values in the conscious group (128 +/- 15, 474 +/- 44, 112 +/- 40, and 7 +/- 3), respectively. O2 extraction did not change after pentobarbital anesthesia. However, the dispersion of venous O2 saturation narrowed. The distribution of O2 saturations in 373 cerebral veins of anesthetized rats had a significantly reduced coefficient of variation [C.V. = 100 x (S.D./mean) = 13] as compared to a C.V. of 18 in 320 veins in conscious rats. Thus, pentobarbital anesthesia reduced the microregional venous O2 saturation inhomogeneity in the brain, creating a more uniform balance of oxygen supply and consumption.

Animals↗

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↗

Diffusion distances, total capillary length and mitochondrial volume in pressure-overload myocardial hypertrophy.

We examined the relationships between blood pressure, coronary blood flow, cardiac output, myofiber growth, capillarity, mitochondrial content, and capillary and mitochondrial distributions in a pressure-overload model of myocardial hypertrophy. The Goldblatt one kidney-one clip (1K1C) procedure was performed on seven adult rabbits. After 1 month, mean blood pressure increased 50% and mean heart mass increased 30%. Coronary blood flow and cardiac output at rest were similar in control and 1K1C hearts; cardiac output fell 40% when 1K1C hearts were paced to 35% above basal heart rate. Capillary density in the left ventricular free wall (LV) decreased with increasing fiber size by as much as 30%. However, capillary-to-fiber ratio and total capillary length in the LV increased with heart size by up to 30% and 80%, respectively. This indicated that there was some proliferation of capillaries taking place, but not enough in comparison to fiber growth to prevent the lengthening of distances between capillaries. Mitochondrial volume density decreased by as much as 30% with increasing heart size, but total mitochondrial volume increased up to 80%. This indicated that there was some proliferation of mitochondria, but not enough to prevent dilution of mitochondria by the growing myofibrillar elements. Analysis of the distribution of mitochondria suggested that the new mitochondrial material was added to the center of myofibers, thereby further lengthening oxygen diffusion distances. There was a constant ratio of 10.4 +/- 0.3 km of capillaries per ml of mitochondria in 1K1C and control hearts, demonstrating that the structures for oxygen supply and consumption were remaining in fixed proportion to each other. There was no evidence that the decreased performance of paced 1K1C hearts was attributable to an oxygen diffusion limitation to mitochondria.

Animals↗

Effects of isoflurane on transport across the blood-brain barrier.

The blood-brain barrier (BBB) plays an important role in regulating and restricting transfer of molecules into the interstitial space of the brain. Anesthetic agents may affect the permeability of the BBB. In this investigation, the effect of isoflurane on the transport of small hydrophilic molecules across the BBB was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area (PS) product. In the control group, after a femoral artery and vein were catheterized under isoflurane anesthesia, rats were allowed to remain awake for 2 h before measuring Ki (n = 6) or rCBF (n = 11). In the two experimental groups, rats were anesthetized with 1% and 2% isoflurane respectively, and their lungs were mechanically ventilated through a tracheal tube. Ki was measured (1% n = 6, 2% n = 7) using 14C-alpha-aminoisobutyric acid, and rCBF was measured (2% n = 7) using 14C-iodoantipyrine. Two percent isoflurane did not affect rCBF in 9 of 13 brain regions. Blood flow was less in the lateral and posterior cortex and greater in the medulla and pons when compared with the control group. Ki was less in 11 of 13 brain regions in both the 1% and 2% isoflurane groups than in the control group. There was no significant difference between 1 and 2% isoflurane in any brain region.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoisobutyric Acids↗

Effect of acetazolamide on cerebral blood flow and capillary patency.

This study investigated the effects 2 h after administration of acetazolamide on cerebral blood flow and the pattern of cerebral capillary perfusion. Arterial blood pressure, heart rate, arterial blood gases, and pH were recorded in two groups of rats along with either regional cerebral blood flow or the percentage of capillary volume per cubic millimeter and number per square millimeter perfused as determined in cortical, thalamic, pontine, and medullary regions of the brain. Blood pressure, heart rate, and arterial PCO2 were not significantly different between the rats receiving acetazolamide (100 mg/kg) and the controls. Arterial blood pH was significantly lower in the acetazolamide rats. Blood flow increased significantly in the cortical (+ 102%), thalamic (+ 89%), and pontine (+ 88%) regions receiving acetazolamide. In control rats, approximately 60% of the capillaries were perfused in all of the examined regions. The percentage of capillaries per square millimeter perfused was significantly greater in the cortical (+ 52%), thalamic (+ 49%), and pontine (+ 47%) regions of acetazolamide rats compared with controls. In the medulla the increases in blood flow and percentage of capillaries perfused were not significant. Thus in the regions that acetazolamide increased cerebral blood flow, it also increased the percentage of capillaries perfused.

Acetazolamide↗

Quantitative determination of morphometric indices of the total and perfused capillary network of the newborn pig brain.

The purpose of this study was to determine if the newborn pig brain had a reserve of unperfused capillaries during normoxia. To accomplish this, a method was developed to determine the volume fraction, surface area, and number of both total and perfused capillaries in the newborn pig brain. Newborn pigs of either sex, 2-7 d old, were used. FITC-dextran, molecular weight 147,000, was used as a plasma marker to visualize the perfused capillaries. Alkaline phosphatase staining was used to stain the total capillary bed of the brain. Our results showed that FITC-dextran stayed within the vascular compartment, as it was not seen in areas that were not subsequently visualized with alkaline phosphatase staining. Eighty-four to 86% of the alkaline phosphatase-stained capillaries could be visualized with perfusion markers (india ink or FITC-dextran) in different brain regions. Similar results were obtained in two animals using a basement membrane stain, silver methenamine. The total volume fraction of capillaries (mm3/mm3) was cortex 0.055 +/- 0.012, cerebellum 0.062 +/- 0.011, and medulla 0.039 +/- 0.012. Capillary surface area (mm2/mm3) of different brain regions averaged cortex 23.2 +/- 1.8, cerebellum 24.8 +/- 2.5, and medulla 15.8 +/- 2.9. The total number of capillaries (per mm2) was cortex 375 +/- 37, cerebellum 329 +/- 37, and medulla 216 +/- 32. The time course of filling of the capillaries indicated that approximately 50% were perfused at 6 s, which increased to over 80% at 12 s and remained unchanged thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of fentanyl on alpha-aminoisobutyric acid transfer across the blood-brain barrier.

The effect of fentanyl on the transfer of small hydrophilic molecules across the blood-brain barrier was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area product. In the control group (n = 14), after a femoral artery and vein were catheterized under isoflurane anesthesia, the rats were allowed to remain awake for 1.5 h before measuring Ki (n = 8) using intravenous 14C-alpha-aminoisobutyric acid or rCBF (n = 6) using 14C-iodoantipyrine. In the fentanyl groups, rats were injected with 25 micrograms/kg (low (n = 6) or 100 micrograms/kg (high dose) of fentanyl (n = 14), followed by a continuous infusion at a rate of 50 or 200 micrograms.kg-1.h-1, respectively. Their lungs were mechanically ventilated. The Ki (low dose, n = 6; high dose, n = 8) and rCBF (high dose, n = 6) were measured 1 h after fentanyl infusion. The Ki was lower in 9 of 13 brain regions in the low-dose fentanyl group and in 7 of 13 brain regions in the high-dose fentanyl group than in the control animals. The average value of Ki in all the brain regions was 8.6 +/- 4.6 microL.g-1.min-1 in the control group, 5.2 +/- 2.9 microL.g-1.min-1 in the low-dose fentanyl group, and 5.7 +/- 2.9 microL.g-1.min-1 in the high-dose fentanyl group. High-dose fentanyl did not significantly affect rCBF in any brain region studied. The value of the regional permeability-surface area product was similar to the corresponding regional Ki in the groups studied. In conclusion, fentanyl decreased the transfer of small hydrophilic molecules across the blood-brain barrier, as demonstrated by a decreased Ki and permeability-surface area product, without significant changes in rCBF.

Aminoisobutyric Acids↗

Influence of an in-patient exercise program on scoliotic curve.

In 107 patients with idiopathic scoliosis radiographs were performed under standard conditions immediately before and immediately after a 4-6 week in-patient exercise program at the Katharina-Schroth Hospital. The average angle of curvature as measured by the Cobb technique was 43.06 degrees (standard deviation = 22.87) before treatment and 38.96 degrees (SD = 23.00) after treatment. An improvement in the curve of 5 degrees or more was found in 43.93% of the patients, 53.27% were unchanged and in 2.8% the curve increased by 5 degrees or more. Altogether the improvements in curvature were highly significant. These results show that even in severe scoliosis the magnitude of the curve can be reduced by a specific rehabilitation program of physiotherapy.

Adolescent↗

[Characteristics of physical therapy of scoliosis patients in adulthood].

Rehabilitation treatment of adult patients with scoliosis essentially is of a secondary prevention orientation. Along with countering curve progression, the main focus is on improving secondary functional impairments of the cardiopulmonary system as well as on the management of scoliosis-induced pain. In-patient physiotherapy rehabilitation provides major impacts in these respects, especially since they have proven their worth in obtaining increases in vital capacity, rib mobility, cardiopulmonary functioning, and in reducing scoliosis-induced pain complaints.

Adult↗

Effect of amphetamine on cerebral blood flow and capillary perfusion.

The purpose of this study was to determine the cerebral regional microvascular and vascular responses to amphetamine sulfate at a dose (5 mg/kg) known to affect neuronal function. Cerebral blood flow (14C-iodoantipyrine method) and percent of perfused capillaries (fluorescein isothiocyanate-dextran and alkaline phosphatase staining method) were determined during control and after intravenous administration of amphetamine in conscious Long-Evans rats. Amphetamine caused an increase in blood pressure (34%) and heart rate (31%). There was a significant increase in averaged cerebral blood flow from 98 +/- 8 to 166 +/- 9 ml/min/100 g after amphetamine. This flow increase was significant in the cortex, basal ganglia, pons and medulla, however the increase was not significant in the hypothalamus. In control rats, there were approximately 325 +/- 17 capillaries/mm2 of brain tissue and 52 +/- 1% of them were perfused. Amphetamine increased the percent perfused significantly to 72 +/- 1% in all examined regions. There was a similar significant increase in the percent of perfused cerebral capillary volume fraction. There were both vascular and microvascular responses to amphetamine, increasing cerebral blood flow as well as reducing the diffusion distance for oxygen.

Amphetamine↗

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↗