Biomedical subjects

H R Weiss

Publications and source records attributed to H R Weiss.

At least 73 records · Page 4Linked to original sources

PubMed1997

cGMP level that reduces cardiac myocyte O2 consumption is altered in renal hypertension.

We tested the hypothesis that cardiac myocytes from hypertensive (one kidney, one clip; 1K,1C) cardiac-hypertrophied rabbits require higher guanosine 3',5'-cyclic monophosphate (cGMP) to similarly lower O2 consumption than control myocytes and that this effect is caused by differences in guanylate cyclase activity. Using isolated myocytes from control and 1K,1C New Zealand White rabbits, we obtained O2 consumption (nl O2 x min(-1) x 10(5) cells) and cGMP (fmol/10(5) cells) levels after stimulation of guanylate cyclase with nitroprusside, CO, or guanylin (10(-8)-10(-5) M). Soluble guanylate cyclase activity was also determined. Basal cGMP was elevated in 1K,1C vs. control (176 +/- 28 vs. 85 +/- 13) myocytes. cGMP increased in 1K,1C and control myocytes after stimulation with nitroprusside, CO, and guanylin. Guanylate cyclase activity in 1K,1C vs. control myocytes was not statistically different. Basal O2 consumption in 1K,1C vs. control myocytes was comparable (307 +/- 1 vs. 299 +/- 22). O2 consumption was similarly decreased when guanylate cyclase was stimulated. Control regression equations correlating cGMP and O2 consumption were O2 consumption = -1.46 x [cGMP] + 444.65 (r = 0.96) for CO, O2 consumption = -0.58 x [cGMP] + 328.48 (r = 0.82) for nitroprusside, and O2 consumption = -1.25 x [cGMP] + 389.15 (r = 0.88) for guanylin. The 1K,1C regression equations were O2 consumption = -1.36 x [cGMP] + 537.81 (r = 0.97) for CO, O2 consumption = -0.23 x [cGMP] + 307.30 (r = 0.88) for nitroprusside, and O2 consumption = -1.27 x [cGMP] + 502.91 (r = 0.89) for guanylin. These data indicate that 1K,1C hypertrophic myocytes had higher cGMP than controls at every level of O2 consumption. This effect was not caused by differences in basal or maximal guanylate cyclase activity.

Animals↗

PubMed1997

Nitric oxide reduces myocardial contractility in isoproterenol-stimulated rat hearts by a mechanism independent of cyclic GMP or cyclic AMP.

Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effects of intracoronary nitroprusside (NP, 1 and 10 mM) in the absence and presence of isoproterenol (ISO, 10(-8) M) on cardiac function, O2 consumption, cyclic GMP and cyclic AMP. ISO, with and without NP, increased cyclic AMP (from 287 +/- 21 to 477 +/- 33 pmol/g) without altering cyclic GMP. Left-ventricular pressure increased from 97 +/- 12 to 178 +/- 9 mm Hg and dP/dtmax from 1,786 +/- 275 to 4,049 +/- 354 mm Hg/s. NP increased cyclic GMP (from 4 to 30 pmol/g) in both the absence and presence of ISO, but NP did not alter cyclic AMP. Without ISO, NP insignificantly altered left-ventricular pressure; however, in the presence of ISO, NP significantly decreased left-ventricular pressure by -25 +/- 4 mm Hg and decreased dP/dtmax by -619 +/- 142 mm Hg/s. Isoproterenol increased O2 consumption, but the changes with NP were not significant. When this study was repeated in the presence of LY83583, a guanylate cyclase inhibitor, NP still produced cardiac depression in the presence of ISO. Therefore, cardiodepressant effects of NP were only observed against a background of inotropic stimulation with ISO. However, effects of NP on contractility were unrelated to increases in cyclic GMP or cyclic GMP-induced changes in cyclic AMP.

Aminoquinolines↗

PubMed1996

Effect of up-regulation of NMDA receptors on cerebral O2 consumption and blood flow in rat.

We tested the hypothesis that cerebrocortical blood flow and O2 consumption would be proportional to an up-regulated number of functional N-methyl-D-aspartate (NMDA) receptors. Previous work had shown a relationship between cerebral metabolism and NMDA receptor activity. We increased the specific binding to NMDA receptors in the cerebral cortex, from 2.2 +/- 0.9 to 4.5 +/- 0.8 (density units) in male Long-Evans rats by daily giving two intraperiotoneal injections (30 mg/kg) of CGS-19755, an NMDA receptor inhibitor, for 7 consecutive days (discontinued for 20 h before experiment). Twelve up-regulated (CGS treated) and 12 control rats were used in this study. Under isoflurane anesthesia and after topical stimulation of the right cerebral cortex with 10(-2) M NMDA, the blood flow (14C-iodoantipyrine method) increased from 98 +/- 11 ml/min/100 g in the unstimulated cortex of the control rats to 161 +/- 37 ml/min/100 g in the stimulated cortex. The unstimulated value for blood flow (95 +/- 7 ml/min/100 g) did not change in the upregulated group but it doubled (194 +/- 69 ml/min/100 g) in the stimulated, upregulated cortex. Similarly, O2 consumption (cryomicrospectrophotometrically determined) in normal rats increased 46%, from 9.3 +/- 1 ml/min/100 g to 13.6 +/- 4 after NMDA stimulation. While in the upregulated animals, O2 consumption increased 103% from 7.9 +/- 0.6 to 16 +/- 6.5 after NMDA stimulation. In conclusion, NMDA receptor upregulation does not alter basal cerebrocortical blood flow or O2 consumption but in the NMDA-stimulated cortex, the blood flow and O2 consumption increase is dependent on the number of NMDA receptors present.

Animals↗

PubMed1996

Increased guanylate cyclase activity is associated with an increase in cyclic guanosine 3',5'-monophosphate in left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) produced by aortic valve plication leads to increased myocardial cyclic GMP. We tested whether this was a result of increased soluble guanylate cyclase activity or nitric oxide (NO) synthase and its functional consequences. We used the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) or the NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME) in 12 control and 12 LVH anesthetized open-chest mongrel dogs. L-NAME (6 mg/kg) or SIN-1 (1 microgram/kg per min) was infused into the left anterior descending coronary artery and regional segment work and cyclic GMP levels were determined. In vitro myocardial guanylate cyclase sensitivity (0.43 +/- 0.04 to 0.28 +/- 0.04 mM [EC50]) and maximal activity (10.1 +/- 2.9 to 25.5 +/- 6.5 pmol/mg protein per min) were significantly increased in LVH as compared with control animals in response to nitroprusside stimulation, but cyclic GMP-phosphodiesterase activity was similar. In LVH dogs, basal cyclic GMP was significantly elevated in vivo when compared with controls. Treatment of dogs with SIN-1 resulted in a significant increase in cyclic GMP in control (1.09 +/- 0.12 to 1.48 +/- 0.19 pmol/gram) and a greater increase in the LVH group (1.78 +/- 0.16 to 3.58 +/- 0.71 pmol/g). L-NAME had no effect on myocardial cyclic GMP levels in control or LVH dogs. Segment work decreased in the control group after SIN-1 (1,573 +/- 290 to 855 +/- 211 grams x mm/min). LVH dogs showed no decrement in work as a result of treatment with SIN-1. L-NAME did not cause significant changes in myocardial cyclic GMP, O2 consumption, or work in either control or LVH dogs, but vascular effects were evident. SIN-1 increased cyclic GMP, and with greater effect on LVH; however, this resulted in a decrement in function only in the control group. The greater increased cyclic GMP in LVH dogs is not related to increased NO production, but is related to significantly higher sensitivity and maximal activity of soluble myocardial guanylate cyclase.

Animals↗

PubMed1996

Cyclic GMP-phosphodiesterase inhibition does not alter cerebral oxygen consumption.

The effect of zaprinast, a cyclic guanosine monophosphate inhibitor, on the level of cyclic GMP and cerebral O2 consumption was determined. Anesthetized male Long-Evans rats were divided into a control group (n = 15) and a zaprinast treated group (n = 15). Vehicle was applied topically to the left cortex and 3*10-3 M zaprinast was applied to the right cortex. A saline treated control group was also studied. Regional cerebral blood flow was determined by [14C]-iodoantipyrine and regional 0(2) extraction was determined by microspectrophotometry. The level of cyclic GMP was measured by radioimmunoassay. There were no hemodynamic or blood gas differences between groups. The level of cyclic GMP was not significantly different between the right and left cerebral cortex of the control group (17.0 + or - 4.3 and 17.7 + or - 4.6 pmol/g). In the zaprinast treated group, there was a significant (46%) increase in the level of cyclic GMP in the zaprinast treated cortex (20.5 + or - 8.1) in comparison to the vehicle treated cortex (14.0 + or - 5.7). Zaprinast did not significantly alter cerebral blood flow. There were no significant differences in regional 0(2) extraction. The 0(2) consumption of the zaprinast treated cortex (8.0 + or - 3.3 ml O(2)*min(-1)*100 g(-1)) was not different from that of the vehicle ) treated cortex (7.0 + or - 2.9) or those of the control group. Thus, our data indicated that the increased level of cyclic GMP had no significant effect on cerebral oxygen consumption.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1996

Cerebral microregional oxygen balance during chronic versus acute hypertension in middle cerebral artery occluded rats.

This study was performed to compare microregional 0(2) supply and consumption balance in spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY), and in phenylephrine-induced acutely hypertensive WKY (WKY + ph) rats. Under isoflurane anesthesia, a middle cerebral artery (MCA) of SHR (n = 7) and WKY (n = 14) rats was occluded. Seven of the WKY rats were infused with phenylephrine (WKY + ph) to keep the mean arterial pressure (MAP) at the same level as that of the SHR. In all animals, 1 h after MCA occlusion, regional cerebral blood flow (rCBF) was determined using an autoradiographic technique, and microregional arterial and venous 02 saturations were determined using microspectrophotometry. MAP was 76 +/- 4 (SD), 136 +/- 15, and 132 +/- 12 mm Hg for the WKY, WKY + ph, and SHR groups, respectively. All variables describing regional O2 balance and rCBF were similar between the SHR and the WKY groups in the ischemic cortex as well as in the contralateral cortex. With phenylephrine infusion, rCBF of both the ischemic cortex and the contralateral cortex were increased in the WKY group. The average 02 supply-to-consumption ratio in the ischemic cortex was higher in the WKY + ph than in the WKY or SHR group. In the ischemic cortex, heterogeneity of venous 02 saturation (SvO2), expressed as a coefficient of variation (CV = 100 X SD/mean), was significantly lower in the WKY + ph (18.3 +/- 2.4) group than in the SHR (30.5 +/- 11.8) or in the WKY (31.3 +/- 9.0) group. The number of veins with low 02 saturation (SvO2 < 40%) in the ischemic cortex was significantly lower in the WKY + ph than in the SHR or in the WKY group. Our data suggest that in chronically hypertensive animals, cerebrovascular adaptations enable the microregional 02 balance in focal ischemia to be maintained at a level similar to that of normotensive animals. However, in normotensive animals with focal cerebral ischemia, an acute increase of MAP improves microregional O2 balance.

Acute Disease↗

PubMed1996

Hydroxyethyl starch solution attenuates blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

This study was performed to investigate whether a fraction of hydroxyethyl starch macromolecules, prepared from pentastarch and known as "Hes-Pz," with molecular weights of 100,000-1,000,000, protects against blood-brain barrier (BBB) disruption due to intracarotid injection of hyperosmolar mannitol. Rats were anesthetized with isoflurane, and retrograde catheterization of a unilateral eternal carotid artery was performed. Except for the Control group (n = 8), hemodilution was performed using lactated Ringer's solution LR group, n = 7), 6% hetastarch (HES group, n = 7), or 6% HES-Pz (HES-Pz group, n = 8) to reduce the hematocrit to about 23%. The BBB transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid was determined after a unilateral intracarotid injection of 25% mannitol. Blood pressure and hematocrit were similar in all groups. In the control group, Ki was increased significantly in the ipsilateral cortex (IC) where mannitol was injected (16.3 +/- 6.1 vs 4.1 +/- 1.4 microL.min-1) when compared with the contralateral cortex (CC). Ki was similar in the CC in all four groups. The Ki in the IC was significantly lower in the HES-Pz(6.4 +/- 3.5 microL.g-1.min-1) than in the Control, HES, or LR group (16.3 +/- 6.1, 19.0 +/- 12.9, 17.9 +/- 10.8 microL.g-1.min-1, respectively). Our data suggest that HES-Pz significantly attenuates disruption of the BBB caused by an injection of hyperosmolar mannitol.

Aminoisobutyric Acids↗

PubMed1996

Increased blood-brain permeability with hyperosmolar mannitol increases cerebral O2 consumption and O2 supply/consumption heterogeneity.

This study was performed to evaluate whether increasing the permeability of the blood-brain barrier by unilateral intracarotid injection of hyperosmolar mannitol would alter O2 consumption and the O2 supply/consumption balance in the ipsilateral cortex. Rats were anesthetized with 1.4% isoflurane using mechanical ventilation. Retrograde catheterization of a unilateral external carotid artery was performed to administer 25% mannitol at a rate of 0.25 ml/kg/s for 30 s. The blood-brain barrier transfer coefficient (K(i) of 14C-alpha aminoisobutyric acid was measured in one group (N = 7) after administering mannitol. Regional cerebral blood flow (rCBF), regional arterial and venous O2 saturation and O2 consumption were measured in another group using a 14C-iodoantipyrine autoradiographic technique and microspectrophotometry (N = 7). Vital signs were similar before and after administering mannitol. K(i) was significantly higher in the ipsilateral cortex (IC) (22.3 +/- 8.4 microliters/g/min) than in the contralateral cortex (CC) (4.4 +/-1.1). rCBF was similar between the IC (105 +/- 21 ml/g/min) and the CC (93 +/- 20). Venous O2 saturation was lower in the IC (43 +/- 7%) than in the CC (55 +/- 4%). The coefficient of variation (100 x SD/mean) of venous O2 saturation was significantly elevated in the IC (32.3) compared with the CC (18.2), indicating increased heterogeneity of O2 supply/consumption balance. O2 consumption was higher in the IC (9.6 +/- 3.0 ml O2/100 g/min) than in the CC (6.7 +/- 1.5). Our data suggested that increasing permeability of the blood-brain barrier increased cerebral O2 consumption and the heterogeneity of local O2 supply/consumption balance.

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

Endogenous basal nitric oxide production does not control myocardial oxygen consumption or function.

Previous studies from our laboratory have shown that an extrinsic nitric oxide (NO) donor (i.e., nitroprusside) caused vasodilatation and negative inotropy by activating guanylate cyclase and increasing myocardial cyclic GMP. We tested the hypothesis that endogenous myocardial NO production would limit myocardial oxygen consumption and function in vivo. We used the NO synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA) in nine open-chest anesthetized mongrel dogs. Either L-NAME (6 mg/kg) or L-NMMA (3 mg/kg) were infused into the left anterior descending coronary artery (LAD). The circumflex (CFX) coronary artery region served as a control. Regional segment work was calculated as the integrated product of local force (miniature transducer) and segment shortening (ultrasonic crystals). Local myocardial O2 consumption was determined using an ultrasonic LAD flow probe and local arterial-venous O2 content difference (oximetry). Cyclic GMP levels were obtained via a radioimmunoassay. Both L-NAME and L-NMMA caused a local decrease in coronary blood flow (LAD flow: 80 +/- 8 to 69 +/- 7 ml/min/100 g [means +/- SEM]) and increased O2 extraction (9.1 +/- 0.6 to 10.2 +/- 0.7 ml O2/100 ml). However, this led to no change in local O2 consumption. LAD segment force was not altered (12.1 +/- 0.7 to 11.6 +/- 0.9 g), nor was the percent shortening changed (10.8 +/- 1.8% to 10.0 +/- 1.4%) by L-NAME or L-NMMA, leading to no net change in segment work. Myocardial cyclic GMP levels were not different in a comparison between the LAD (1.7 +/- 0.4 pmoles/g) and control (1.7 +/- 0.2) regions with either L-NAME or L-NMMA. We conclude that blockade of endogenous NO production with L-NAME and L-NMMA is sufficient to cause vasoconstriction in the heart of anesthetized dogs. However, this dose did not lead to alteration in local myocardial function, O2 consumption, or cyclic GMP levels.

Acetylcholine↗

PubMed1996

Effects of hemorrhagic hypotension on cerebral blood flow and perfused capillaries in newborn pigs.

We examined the effect of hemorrhagic hypotension on cerebral blood flow and perfused capillaries in newborn pigs, 2-10 days old. Cerebral blood flow was measured by using radioactive microspheres, perfused capillaries were determined by infusing a plasma marker, fluorescein isothiocyanate (FITC) - dextran (molecular mass 147,000 Da), and total capillaries were determined by staining with alkaline phosphatase. Rapid removal of 66 +/- 16 mL of blood resulted in a fall in mean blood pressure from 68 +/- 6 to 31 +/- 4 mmHg (1 mmHg = 133.3 Pa), an increase in heart rate from 137 +/- 18 to 240 +/- 34 beats/min, and a drop in arterial pH from 7.33 +/- 0.05 to 7.23 +/- 0.07. PCO2 was controlled by mechanical ventilation (36 +/- 4 mmHg before hemorrhage and 35 +/- 5 mmHg after hemorrhage) and PO2 remained stable (89 +/- 11 mmHg before hemorrhage and 94 +/- 10 mmHg after hemorrhage). Blood flow (n = 9) did not fall significantly in any brain region after hemorrhage. The percentage of perfused capillaries/mm2 (control, n = 7, hemorrhage, n = 6) was reduced in all brain regions during hypotension (cortex from 72 +/- 8 to 57 +/- 8%, cerebellum from 75 +/- 10 to 52 +/- 10%, and medulla from 76 +/- 8 to 51 +/- 9%). Similar results were seen for perfused capillary surface area We conclude that hemorrhagic hypotension resulted in a variable blood flow response with no significant reduction in cerebral blood flow but a reduction in perfused capillary number and surface area in all brain regions studied. We speculate that decreased capillary perfusion may be a contributing factor in diffuse neuronal injury after severe hemorrhagic hypotension.

Animals↗

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

Effect of nitroprusside on regional cerebral cyclic GMP, blood flow and O2 consumption in rat.

This investigation was conducted to test whether topical nitroprusside (NP), a cytosolic guanylate cyclase activator, would increase the level of cyclic GMP and alter O2 consumption or blood flow in the cerebral cortex of rats. Male Long-Evans rats were used in a control (n = 9), low dose NP (n = 13, 10(-3) M) or high dose NP (n = 12, 10(-2) M) group. Nitroprusside or saline was topically applied to the right side of the cerebral cortex and the left side was used as a control. The cyclic GMP level was determined in five rats in each group using a radioimmunoassay. In the other rats in each group, regional cerebral blood flow was measured by [14C]iodoantipyrine and regional arterial and venous O2 saturations were determined microspectrophotometrically. Nitroprusside significantly increased the cyclic GMP level from 21.4 +/- 12.0 pmol/g (contralateral cortex) to 52.2 +/- 36.7 pmol/g (NP treated cortex) in low dose nitroprusside group and from 19.9 +/- 22.6 pmol/g (contralateral cortex) to 58.5 +/- 15.1 pmol/g (NP treated cortex) in high dose nitroprusside group. High dose nitroprusside significantly increased cerebral blood flow from 80 +/- 11 ml.min-1.100 g (contralateral cortex) to 114 +/- 11 ml.min-1.100 g (NP treated cortex). However, there was no significant difference in O2 extraction and O2 consumption between the NP treated cortex and contralateral cortex in either the low or the high dose NP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Myocardial venous O2 saturation becomes more heterogeneous during hypoxic and carbon monoxide hypoxia.

The hypothesis tested was that myocardial venous O2 saturation (SvO2) heterogeneity, a measure of microregional O2 supply/consumption balance, would increase under hypoxic and CO-hypoxia conditions. Since we are able to determine both O2 supply and the O2 supply/consumption ratio, we could also determine whether regional myocardial O2 consumption was heterogeneous. Twenty open-chest anesthetized dogs were studied under control and four hypoxic conditions, hypoxic hypoxia induced by ventilation with either an 8% O2 (SaO2 = 56%) or a 6% O2 (SaO2 = 40%) gas mixture for 20 min, or CO hypoxia induced by ventilation with a 1% CO gas mixture for either 7 min (SaO2 = 67%) or 20 min (SaO2 = 40%). Regional myocardial blood flow was measured using radioactive microspheres in 40 pieces (approximately 0.5 g) of the left ventricular free wall. Arterial and venous O2 saturations were determined with a four-wavelength microspectrophotometric method. A total of 28 veins (20-100 microns) were examined to determine SvO2 for each condition within each animal. The coefficient of variation (CV = SD/mean x 100), an index of heterogeneity, was calculated for both flow and SvO2 under each condition. Flow increased with increasing severity of hypoxia but its heterogeneity did not change with hypoxic or CO hypoxia. However, SvO2 heterogeneity significantly increased with increasing severity of hypoxia. A linear regression of SvO2 CV and mean SvO2 showed a significant correlation (CV = -0.84 (mean SvO2) + 51.1, R = 0.59). All possible myocardial O2 consumptions were calculated by multiplying all of the flows and O2 extractions. In 53 subepicardial and subendocardial measurements, only 10% of the flow and O2 supply/consumption heterogeneity observations could be explained by uniform O2 consumption if our acceptance criterion was 0.06-0.1 ml O2/min/100 g, and 50% could be explained with an acceptance criterion of 0.3-0.4 ml O2/min/100 g. Therefore, there must be some regional myocardial O2 consumption heterogeneity. The increase in venous O2 saturation heterogeneity during hypoxia may be due to increased variation in regional myocardial O2 consumption or variation in the control of O2 supply/consumption coupling.

Animals↗

PubMed1995

Measurement of vertebral rotation: Perdriolle versus Raimondi.

The measurement of vertebral rotation according to Perdriolle is widely used in the French-speaking and Anglo-American countries. Even in this measurement technique there may be a relatively high estimation error because of the not very accurate grading in steps of 5 degrees. The measurement according to Raimondi seems to be easier to use and is more accurate, with 2 degrees steps. The purpose of our study was to determine the technical error of both measuring methods. The apex vertebra of 40 curves on 20 anteroposterior (AP) radiographs were measured by using the Perdriolle torsion meter and the Regolo Raimondi. Interrater and intrarater reliability were computed. The thoracic Cobb angle was 43 degrees, the lumbar Cobb angle 36 degrees. The average rotation according to Perdriolle was 19.1 degrees thoracic (SD 11.14), 12.7 degrees lumbar (11.21). Measurement of vertebral rotation according to Raimondi showed an average rotation of 20.25 degrees in the thoracic region (11.40) and 13.4 degrees lumbar (10.92). The intrarater reliability was r = 0.991 (Perdriolle) and r = 0.997 (Raimondi). The average intrarater error was 1.025 degrees in the Perdriolle measurement and 0.4 degrees in the Raimondi measurement. Interrater error was on average 3.112 degrees for the Perdriolle measurement and 3.630 degrees for the Raimondi measurement. This shows that both methods are useful tools for the follow-up of vertebral rotation as projected on standard X-rays for the experienced clinical. The Raimondi ruler is easier to use and is slightly more reliable.

Humans↗

PubMed1995

Effects of CAS 754, a new nitric oxide donor, on regional cerebral blood flow in focal cerebral ischemia.

Nitric oxide (NO) plays an important role in regulating regional cerebral blood flow (rCBF). This study was performed to compare the effects of the NO donor, CAS 754, a sydnonimine derivative, and sodium nitroprusside (SNP) on rCBF in ischemic and nonischemic brain regions. Twenty-eight rats were anesthetized with 1.4% isoflurane and were mechanically ventilated. A middle cerebral artery (MCA) was occluded in each animal. In the CAS 754 group (n = 7), 40 min after MCA occlusion, 4-6 mg/kg of CAS 754 was administered intravenously (i.v.) to decrease the mean arterial blood pressure (MAP) to 55-60 mm Hg. In the SNP group (n = 7), an infusion of SNP was started to decrease the MAP to the same level as that of the CAS group. In the CAS-Ph group (n = 7), phenylephrine was infused after CAS754 had been administered in order to maintain the MAP at the control level (95-100 mm Hg). The remaining seven rats were used as a control group. rCBF was measured using 14C-iodoantipyrine in all four groups of animals 1 h after MCA occlusion (20 min after the start of drug administration). The average rCBF of the nonischemic brain regions (121 +/- 15 mL.min-1.100 g-1) was increased by 34% with CAS 754 (162 +/- 39 mL.min-1.100 g-1). However, SNP did not significantly change the average rCBF of the nonischemic brain regions (114 +/- 5 mL.min-1.100 g-1). Neither CAS 754 nor SNP significantly affected the rCBF of the ischemic cortex (control 51 +/- 7, CAS 61 +/- 13, SNP 53 +/- 18 mL.min-1.100 g-1). Phenylephrine infusion in the CAS 754-treated animals did not significantly affect the rCBF of the ischemic or nonischemic brain regions. In conclusion, our study demonstrated that CAS 754 was a more effective cerebral vasodilator than nitroprusside when administered systemically. In the ischemic cortex, neither CAS 754 nor nitroprusside improved rCBF Failure of CAS 754 to improve the rCBF of the ischemic cortex does not appear to be due to hypotension induced by CAS 754.

Animals↗

PubMed1995

Myocardial metabolic and functional responses to acetylcholine are altered in thyroxine-induced cardiac hypertrophy.

We tested the hypothesis that acetylcholine would reduce myocardial O2 consumption and function, and that thyroxine (T4, 0.5 mg/kg for 16 days) induced cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand white rabbits were divided into four groups: control-vehicle (CV, n = 8), control-acetylcholine (CA, n = 10), T4-vehicle (T4V, n = 9), and T4-acetylcholine (T4A, n = 10). Either vehicle or acetylcholine (10(-3) M) was topically applied to the left ventricular surface. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption, and muscarinic receptor density and affinity were also determined. T4 increased the heart weight/body weight ratio from 2.6 +/- 0.1 to 3.4 +/- 0.1. T4-treated animals had higher heart rates, blood pressures, and left ventricular dP/dtmax than control rabbits. Topical acetylcholine depressed hemodynamic parameters with a greater decrement in pressures and cardiac output in the T4A group (CA, -25%, T4A, -40%). Myocardial O2 consumption and coronary blood flow were higher in the T4-treated hearts. Myocardial O2 consumption significantly declined in both groups during acetylcholine, but the reduction was greater in the T4-treated hearts (CV 7.9 +/- 0.4 to CA 5.8 +/- 0.6 and T4V 18.8 +/- 3.0 to T4A 7.3 +/- 1.0 mL O2.min-1.100 g-1). Muscarinic receptor density (Bmax) was elevated by 41% in the T4-treated hearts, but affinity (Kd) was not altered. Thus, the T4-treated hearts responded to acetylcholine to a greater extent than control hearts in terms of functional and O2 consumption decrements.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1995

Relationship between cGMP and myocardial O2 consumption is altered in T4-induced cardiac hypertrophy.

We tested the hypothesis that increases in guanosine 3',5'-cyclic monophosphate (cGMP) would reduce myocardial O2 consumption and that thyroxine (T4)-induced (0.5 mg/kg for 16 days) cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand White rabbits were divided into four groups: control vehicle (CV, n = 7), control nitroprusside (CN, n = 6), T4 vehicle (T4V, n = 8), and T4 nitroprusside (T4N, n = 8). Vehicle or sodium nitroprusside (10(-4) M) was topically applied to the left ventricular subepicardium for 15 min. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Guanylate cyclase activity and cGMP were determined by radioimmunoassay. T4 increased the heart weight-to-body weight ratio from 2.7 +/- 0.1 to 3.4 +/- 0.2. Topical application of nitroprusside had no significant hemodynamic effects. Nitroprusside significantly increased myocardial cGMP in control hearts (CV = 4.1 +/- 0.3 to CN = 12.4 +/- 5.0 pmol/g) and T4 hearts (T4V = 3.9 +/- 0.3 to T4N = 5.2 +/- 0.4). The increase in the level of myocardial cGMP was significantly greater in CN (+202%) than in T4N (+33%). There were no significant differences in basal or total guanylate cyclase activity between control and T4 rabbits. Myocardial O2 consumption significantly declined in both groups during nitroprusside (10.8 +/- 1.4 for CV to 7.3 +/- 1.0 for CN (-32%) and 13.6 +/- 1.2 for T4V to 9.9 +/- 1.4 ml O2.min-1.100 g-1 for T4N (-27%).(ABSTRACT TRUNCATED AT 250 WORDS)

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