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Biomedical subjects

H R Weiss

Publications and source records attributed to H R Weiss.

At least 181 records · Page 10Linked to original sources

Control of the heterogeneity of O2 saturation in small myocardial veins.

There is a wide variability in the measured O2 saturations (SvO2) of small myocardial veins (20-100 microns). The purpose of the present study was to examine several factors that contributed to this variability. Studies were conducted on anesthetized open-chest dogs. The role of beta-adrenoceptors and flow in the control of the heterogeneity of SvO2 was assessed. The hearts were quick-frozen in liquid N2 and the SvO2 in the subepicardial and subendocardial (ENDO) regions of the left ventricule was determined by microspectrophotometry. Under control conditions, ENDO SvO2 averaged 35% with a variance of 337. The control variance was much more than that of the methodological errors. With propranolol or practolol, variance was reduced by about half, e.g. ENDO SvO2 variance was 145 with propranolol. This reduction in SvO2 variance could be prevented by isoproterenol. When flow is reduced by partial occlusion the SvO2 values were skewed toward lower saturations. When nitroglycerin is administered during this partial occlusion, the SvO2 distribution is restored toward normal. It can be concluded that some of the variability of SvO2 in the heart is control by beta 1-adrenoceptors. There also appears to be an inverse relationship between coronary blood flow and SvO2 heterogeneity. Further work is necessary to determine what other factors control the variability of SvO2.

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Quantitative morphometric determination of arteriolar and capillary perfusion within ischemic rabbit left ventricle.

The aim of this study was to identify the percentage of the capillary and arteriolar beds that was perfused at a given time or that was capable of being perfused within subepicardium and subendocardium of ischemic and nonischemic myocardium of anesthetized, open-chest rabbits. Fluorescein isothiocyanate-dextran (150,000 MW) was injected intravenously to label perfused microvessels of rabbits that were subjected to 60 min of coronary artery occlusion. Fluorescent microscopy was used to identify the perfused vessels and an alkaline phosphatase stain was employed to locate the total microvasculature. Stereological principles were utilized to determine various morphometric parameters. After 14 sec of dextran injection, approximately 66 +/- 2% (mean +/- SEM) of the capillaries and 65 +/- 5% of the arterioles (19-50 microns) were perfused within ischemic myocardium. Two minutes after dextran injection, 72 +/- 3% of the capillaries and 94 +/- 4% of the arterioles were perfused within the ischemic myocardium. In the nonischemic myocardium, 64 +/- 2% of the capillaries and 59 +/- 5% of the arterioles were perfused 14 sec after dextran injection, while 94 +/- 1% and 96 +/- 2% of the capillaries and arterioles, respectively, were perfused 2 min after dextran injection. It is concluded that a significant unperfused reserve of arterioles exists, but a significant portion of the capillary bed is incapable of being perfused within ischemic rabbit myocardium.

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Effect of hypercapnia on coronary circulation.

The relative importance of hypercapnia in the control of coronary circulation was examined in 42 anaesthetised open chest rabbits. Coronary blood flow was determined with 15 micron radioactive microspheres. When mean (SD) Paco2 was increased from 38(10) to 76(16) mm Hg in six rabbits, the hypercapnia caused a 62% increase in coronary blood flow. When a similar degree of metabolic acidosis was induced in 12 rabbits for either 15 or 60 min, no changes in coronary blood flow occurred. No increases in coronary blood flow occurred during hypercapnia with propranolol, 2 mg/kg (n = 12), with or without atrial pacing to maintain heart rate. Similarly, carotid denervation prevented the carbon dioxide induced increase in coronary blood flow in six rabbits. Haemodiluted rabbits (n = 6) with a 40% replacement of blood showed no changes in coronary blood flow with hypercapnia. This was due to the 22% decrease in systolic pressure-time index, despite their intact sympathetic nervous system and reduced Bohr shift. Therefore, although carbon dioxide is a coronary vasodilator, both direct vasodilatation and sympathetic adrenergic activation must be intact in order for coronary blood flow to be increased.

Acidosis↗

Effect of aortic constriction on the oxygen supply-consumption balance in partially ischaemic myocardium.

A study was carried out to determine the effect of distal aortic constriction on the regional oxygen supply-consumption balance in ischaemic and non-ischaemic myocardium. Left anterior descending coronary artery flow was reduced by 50% in anaesthetised mongrel dogs, and half these animals were subjected to distal ascending aortic constriction (ventricular systolic-aortic systolic pressure gradient 50 mm Hg). Blood flows were determined using radioactive microspheres, and arterial and venous oxygen saturations were determined using microspectrophotometry. When left anterior descending artery flow was decreased by 50% tissue flow, as measured by microspheres in the ischaemic region in both control and aortic constricted animals, decreased. Aortic constriction increased flow in the non-ischaemic zone compared with the same region in control animals. The arteriovenous oxygen content difference increased similarly in the ischaemic region in control and aortic constricted animals compared with their respective non-ischaemic zones. Aortic constriction decreased this difference in the non-ischaemic region compared with these same regions in control animals. Oxygen consumption in the non-ischaemic and ischaemic regions of aortic constricted animals was higher than in control animals. The oxygen supply to consumption ratio was lower in the ischaemic zone in both control and aortic constricted animals than in their respective non-ischaemic regions. Aortic constriction does not appear to alter the oxygen supply-consumption balance in the ischaemic myocardium compared with control animals. Thus the increased work performed by the heart in response to the aortic constriction is adequately matched by an increased flow even in the flow restricted region.

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Effect of hypoxia on percent of arteriolar and capillary beds perfused in the rat brain.

The effects of moderate and severe hypoxia on quantitative regional morphometric indexes of the total and perfused arteriolar and capillary network were studied in the rat brain to determine whether diffusion distances were reduced in hypoxia. Fluorescein isothiocyanate (FITC)-labeled dextran was injected into the femoral vein of conscious control and hypoxic rats. After 20 s, the animal was decapitated and the head was frozen in liquid N2. Sections from eight brain regions were photographed to detect the perfused microvessels and then stained for alkaline phosphatase to visualize the total vascular network. There were significant increases in percent perfused arteriolar and capillary morphology between the two groups of hypoxic animals and control animals. In control rats, the percent of capillaries perfused averaged 45.6 +/- 0.6% (mean +/- SE). In moderate hypoxia 63.4 +/- 1.8% of the vessels were perfused and in severe hypoxia 89.4 +/- 0.1% were perfused. The percentage of arterioles perfused changed similarly. There were no significant differences in any index of total or percent perfused arteriolar or capillary morphometry among the regions within any group. During severe hypoxia, a greater percentage of the capillary reserves was utilized. These results demonstrate a uniform response to hypoxia in the capillary and arteriolar network of the conscious rat brain.

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Effect of hemorrhage on regional morphometric indexes of cerebral capillarity.

This study was performed to determine whether the brain can increase the number of perfused capillaries and arterioles supplying it regionally during hemorrhage. This was done using a technique to simultaneously determine total and perfused regional arteriolar and capillary morphology. Conscious Long-Evans rats served as unbled controls or were bled 65 mmHg or to 40-45 mmHg and stabilized for 30 min. Regional cerebral blood flow was determined using [14C]iodoantipyrine in half of these animals and fluorescein isothiocyanate-dextran was injected in the other half for determination of perfused cerebral microvascular morphometric indexes. The total microvasculature was labeled postmortem via an alkaline phosphatase stain. Regional cerebral blood flow was significantly increased in animals bled to 65 mmHg. During hemorrhage to 40-45 mmHg, cerebral blood flow was reduced 50% (from 59 +/- 28 to 26 +/- 11 ml X min-1 X 100 g-1, mean +/- SD) with no regional redistribution. For all treatments, total capillary density ranged from 400 to 500 capillaries/mm2, and in controls 47% were perfused. Animals bled to 65 mmHg did not mobilize their unperfused microvascular reserve even though they showed a slight tendency to do so. During hemorrhage to 40-45 mmHg, this percent increased significantly to 57% with the largest increase occurring in the pons. Approximately 51% of arterioles were perfused in controls and this was not different compared with the percent perfused during hemorrhage. Despite the overall lack of mobilization of unperfused arterioles, some regions within the brain significantly mobilized their reserves with severe hemorrhage, e.g., hippocampus (78%), hypothalamus (67%), and medulla (73%).(ABSTRACT TRUNCATED AT 250 WORDS)

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Beta adrenoceptor control of the microvascular reserve in rabbit myocardium.

This study was performed to determine if the unperfused microvascular reserve in the rabbit heart can be controlled by beta adrenoceptors. Anesthetized, open chest rabbits (N = 54) were subjected to saline i.v., 0.7 mg/kg of atenolol i.v., 1 mg/kg of practolol, 0.1 microgram/kg of salbutamol, 1 microgram/kg of salbutamol or 0.7 mg/kg of atenolol + 1 microgram/kg of salbutamol treatments. In half these animals coronary flows were determined before and after treatment using radioactive microspheres. The others were given 100 mg/kg of fluorescein isothiocyanate-dextran and the hearts were removed and analyzed for perfused and total microvascular morphology. The fluorescence marked the perfused microvessels and the slides were stained to show all vessels. Control group blood flow was 213 +/- 25 ml/min/100 g. Flows decreased 25% with atenolol and practolol whereas no change was seen with salbutamol or atenolol + salbutamol. Total capillary volume fraction ranged from 0.15 to 0.20 mm3/mm3 with 60% of this perfused in controls. Atenolol significantly reduced this to 47% whereas practolol (90%), high-dose salbutamol (97%) and salbutamol + atenolol (99%) resulted in a significant mobilization. Low-dose salbutamol resulted in a mobilization of capillaries to a degree intermediate (79%) between controls and high-dose salbutamol. Total arteriolar volume fraction ranged from 0.002 to 0.004 mm3/mm3 and in controls 65% of this was perfused. This percentage was reduced with atenolol and significantly increased with all other treatments except practolol. Thus, blockade of beta-1 adrenoceptors results in decreases in the percentage of perfused microvessels whereas stimulation of beta-2 adrenoceptors results in an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗

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

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

Animals↗

Effect of locus coeruleus stimulation on regional cerebral oxygen consumption in the cat.

Regional cerebral oxygen consumption was determined during stimulation of the intra-axial noradrenergic pathway to quantitate the metabolic effects of this manipulation on cerebral oxygen extraction, cerebral blood flow (CBF) and its regional distribution. Regional arterial and venous oxygen saturation were examined microspectrophotometrically. Regional CBF was examined using radioactively tagged microspheres (15 +/- 3 microns in diameter). Oxygen consumption was calculated as the regional product of CBF and oxygen extraction. Bipolar concentric electrodes were stereotaxically implanted bilaterally in the locus coeruleus of alpha-chloralose anesthetized, artificially respired adult mongrel cats. The control group was killed after hemodynamic and CBF measurements were taken. The experimental group was sacrificed after these same measurements were taken before and during 10 min of bilateral locus coeruleus stimulation. The cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic blood pressure was significantly increased during treatment. The heterogeneity of venous oxygen saturation was significantly reduced by stimulation. Average CBF and oxygen consumption were significantly decreased to 57% and 59% of control, respectively. Oxygen consumption was significantly reduced in the hypothalamus from 1.5 +/- 0.3 to 0.9 +/- 0.3 ml O2/min/100 g and from 3.5 +/- 0.9 to 1.2 +/- 0.4 ml O2/min/100 g in the cerebellum by treatment. Changes in the neuronal and/or synthetic cerebral activity produced regional decreases in cerebral oxygen consumption and secondarily altered CBF. These changes are probably due to interaction of the intraparenchymal noradrenergic pathways with other systems or processes in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

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The effect of graded doses of norepinephrine on the O2 supply/consumption balance in ischemic and nonischemic rabbit myocardium.

The purpose of this study was to determine the effect of graded doses of norepinephrine on the regional O2 supply/consumption ratio in ischemic rabbit hearts. Open chested, anesthetized rabbits were used and regional flows, O2 extraction, consumption and O2 supply/consumption ratios were determined before and 1 h after occlusion of the left anterior descending coronary artery in controls and animals given 0.1, 1.0 and 10 micrograms/kg per min norepinephrine (NE). After occlusion in controls, mean myocardial blood flow decreased 40% in the occluded region. Blood flow was also depressed in the occluded region for all NE doses compared to their own preocclusion values, but was higher in these regions compared to control animals. O2 extraction was higher in the occluded region compared to the nonoccluded region for all groups; however these values were lower in the NE groups compared to controls. NE increased O2 consumption in the occluded and nonoccluded regions compared to control group values. The O2 supply/consumption ratio was depressed in the occluded region in all groups compared to the nonoccluded region, though no differences were seen between NE and control groups. Thus, increases in the blood flow to the occluded region were proportional to the increases in O2 consumption with infusion of NE, indicating that a reserve exists and can be utilized with NE.

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Dependence of spatial heterogeneity of myocardial blood flow on mean blood flow rate in the rabbit heart.

The relationship between spatial heterogeneity of myocardial blood flow and the rate of perfusion was examined in anaesthetised-chest rabbits. Blood flow determinations employed the radioactive microsphere technique. Five tissue samples were obtained from each of four regions of the left ventricle: left septum, right septum, subendocardium and subepicardium. Standard deviation (SD) and the coefficient of variation (CV = SD/mean flow x 100), an index of spatial heterogeneity, were computed. A wide range of mean coronary flows was obtained in seven groups by inspiration of room air, 8% O2, 8% O2 and 10% CO2, 100% O2, 100% O2 and hyperventilation, and by administration of adenosine or chromomar HCl. Significant differences in CV were found between treatment groups at the upper and lower ends of the flow range. A significant positive linear correlation between overall SD and mean coronary flow was found (r = 0.760). A significant inverse linear relationship between CV and mean flow was found over the entire range of flows studied (r = -0.482). An improved correlation between CV of calculated coronary vascular resistance and mean vascular resistance (r = 0.742) amongst these treatments suggests that spatial heterogeneity is better described by the variability in calibre of large arterioles. This decreased heterogeneity accompanying high flows or reduced vascular resistance may be beneficial in terms of O2 supply and demand under conditions of myocardial stress.

Adenosine↗

Morphometric study of the total and perfused arteriolar and capillary network of the rabbit left ventricle.

A method has been developed to simultaneously and regionally determine several morphometric indices of both the total and perfused arteriolar and capillary beds of the rabbit heart on a quantitative basis. A high molecular weight fluorescein isothiocyanate (FITC) dextran, was injected into the femoral vein of an anaesthetised open chest rabbit. The hearts were removed and frozen in liquid N2 within 14 s after this injection. Sections, 2 micrometers thick, were obtained from the left ventricular wall and the fluorescence photographed to detect perfused arterioles and capillaries. The sections were then stained to visualise the total arteriolar and capillary network. Standard morphometric techniques were employed to study the total and perfused microvasculature. The method was validated to show that it did not alter the microvasculature of the heart, that both the total and perfused microvasculature could be visualised, and that there was little tissue shrinkage. The study found no significant subepicardial vs subendocardial differences in either the total or perfused capillary of arteriolar networks. The total capillary bed had very much larger morphometric indices than the total arteriolar bed. The percentage of the microvasculature perfused ranged from 55 to 64% of the capillary and 51 to 56% of the arteriolar beds for the various indices. Thus at least a part of the control of capillary perfusions is at the level of the arteriole. There was an almost twofold functional reserve in the microvasculature of the heart which could be mobilised by asphyxia.

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Effect of pacing on oxygen supply-to-consumption ratio in ischemic myocardium.

This study was performed to determine if the partially occluded myocardium could maintain its O2 supply-to-consumption ratio during atrial pacing. In 14 open-chest anesthetized dogs, the left anterior descending coronary artery was occluded to 50% of base-line flow, and in half of the dogs the hearts were paced to 50% above base-line heart rate. Blood flows were determined by use of microspheres before and after occlusion, and O2 supply-consumption variables were determined by use of microspectrophotometry. After occlusion in control and paced groups, blood flow was depressed in the ischemic region compared with the nonischemic region. In paced animals, blood flows in all regions were significantly higher compared with their respective values in nonpaced animals. After pacing, mean O2 consumption was 34% higher (53% in the occluded region) compared with control animals. The O2 supply-to-consumption ratio was similar in the occluded region of paced animals compared with the same region in controls. This ratio was lower in ischemic regions of both groups compared with their respective nonischemic regions. This indicates that, despite a reduced O2 supply-to-consumption ratio in the ischemic area, an unutilized reserve of flow exists.

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Effect of ibuprofen and indomethacin on the O2 supply/consumption balance in ischemic rabbit myocardium.

The purpose of this study was to determine if differences in the cardioprotective abilities of ibuprofen and indomethacin were due to their differing abilities to alter the O2 supply/consumption ratio in the ischemic myocardium. Experiments were done on 21 anesthetized open-chest rabbits. Regional flow (using radioactive microspheres), O2 extraction, O2 consumption, and O2 supply/consumption ratio were determined 1 hr after occlusion of the left anterior descending coronary artery in controls and animals given iv 10 mg/kg ibuprofen or iv 3 mg/kg indomethacin. Myocardial blood flow was depressed in the occluded region compared to the nonoccluded region after occlusion for all treatments. O2 extraction in the occluded region was elevated compared to the nonoccluded region for all treatments after occlusion. No differences in O2 consumption were noted between any treatment within the occluded or nonoccluded regions. The O2 supply/consumption ratio was lower in the occluded region compared to the nonoccluded region for all treatments. No differences in this ratio were noted between any treatment. Thus, the effects of indomethacin or ibuprofen on ischemia are not related to acute changes in myocardial O2 supply/consumption balance.

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Immediate vs. long-term desmethylimipramine or chlorimipramine: effects on regional cerebral blood flow.

The immediate vs. long-term effects of desmethylimipramine (DMI) or chlorimipramine (CMI) on cerebral blood flow (CBF) were determined in 17 rabbit brain regions using radioactively tagged microspheres (15 +/- 3 micron in diameter). A single administration of either drug did not alter average CBF or its regional distribution 1 h later. Desmethylimipramine, an agent which primarily blocks re-uptake in presynaptic noradrenergic neurons, significantly increased CBF when administered daily for 21 consecutive days. The regional effects of DMI were not restricted to those areas dense in noradrenergic receptors. Flow was significantly increased in the hypothalamus, olfactory cortex, globus pallidus-putamen and midbrain. These flow increases probably reflect integrated cerebral metabolic, synthetic and/or functional activity which were associated with altered receptor sensitivity and/or number, rather than a direct cerebral vasodilatory effect. In contrast, CMI, a tricyclic antidepressant which primarily blocks presynaptic re-uptake in serotonergic neurons, and produced sedation, had little effect on CBF when administered daily for 21 consecutive days. The immediate effects of these agents on presynaptic re-uptake was not associated with altered CBF. The long-term antidepressant activity of these two agents on receptor sensitivity was probably not correlated with CBF, as evidenced by the lack of effect which CMI had on this parameter. Rather, CBF response appears to be correlated with the therapeutic spectrum of DMI which increases psychomotor activity in retarded depression.

Animals↗

Effect of morphine on regional cerebral oxygen consumption and supply.

The effects of acute opiate receptor stimulation on regional cerebral oxygen consumption and blood flow were examined in 9 regions of the artificially respired, alpha-chloralose-anesthetized cat. Regional cerebral arterial and venous oxygen saturation were examined microspectrophotometrically and regional cerebral blood flow was monitored using radioactively tagged microspheres (15 +/- 3 micron in diameter). Oxygen consumption was calculated as the product of flow and oxygen extraction. In 8 cats, after control cerebral blood flow was obtained, and in 8 experimental cats after this same measurement was obtained before and 40 min after the administration of 1.5 mg/kg morphine sulfate; the cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic and diastolic blood pressure were significantly decreased by treatment. The heterogeneity of venous oxygen saturation was significantly reduced by morphine. Average cerebral blood flow, oxygen extraction and consumption were not altered significantly by morphine. Regional cerebral blood flow in the hypothalamus, thalamic oxygen extraction, and hypothalamic and thalamic oxygen consumption were significantly decreased by treatment. This low dose of morphine may produce changes in cerebral neuronal and/or synthetic activity which lowers oxygen consumption in some regions rich in opiate receptors, while not affecting overall brain oxygen supply or consumption.

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Effect of T4-induced cardiac hypertrophy on O2 supply-consumption balance during normoxia and hypoxia.

The purpose of this study was to determine if thyroxine-induced hypertrophic hearts can maintain an adequate O2 supply-consumption balance both at rest and under hypoxic stress. New Zealand White rabbits were given 0.5 mg/kg L-thyroxine (T4) for 3 or 16 days, and a third group served as a control. Chests were opened under anesthesia, and myocardial blood flow was determined using microspheres. In half of these animals, microspectrophotometric determinations were made on left ventricular arterial and venous O2 saturation, and by combining this data with blood flows, O2 consumption was determined. The other animals were then subjected to hypoxia (8% O2 in N2), and flows and O2 consumption were again determined. T4 increased arterial pressure and heart rate in normoxic animals and also increased myocardial blood flow 65 and 210% for 3- and 16-day T4 groups, respectively, with no regional differences. O2 extraction was also increased in T4 animals. O2 consumption increased 134 and 280% in 3- and 16-day T4 groups. Only normoxic saline controls had a regional O2 consumption difference with subendocardial O2 consumption higher than subepicardial values. When compared with their respective normoxic groups, blood flow increased 49 and 101% for the hypoxic 3- and 16-day T4 groups. Hypoxia had no effect on saline control blood flow. Hypoxia decreased O2 extraction 29 and 41%, respectively, in the 3- and 16-day T4 groups and was unchanged in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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