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Biomedical subjects

H R Weiss

Publications and source records attributed to H R Weiss.

At least 199 records · Page 11Linked to original sources

Effect of hypoxic-hypocapnia on cerebral regional oxygen consumption and supply.

The effect of hypoxic-hypocapnia (PaO2, 35 mm Hg, PaCO2, 22 mm Hg) on regional cerebral O2 consumption and supply was determined in 18 alpha-chloralose-anesthetized open-chest adult cats. Regional arterial and venous O2 saturation measurements determined by a microspectrophotometric technique were combined with regional flow measurements by the radioactive microsphere method to calculate cerebral regional O2 consumption. In a control group, after blood flow was determined with 15 +/- 3-microns-diameter microspheres, the heads were quick-frozen and measurements of flow and arterial-venous O2 differences were obtained from nine brain regions. In the experimental group, similar measurements were obtained after the induction of hypoxic-hypocapnia. Cerebral blood flow was significantly lower than the control group during hypocapnia. Cerebral blood flow increased with the induction of hypoxia. Arterial and venous O2 saturation decreased uniformly and to the same extent in the nine examined brain regions. This maintained the arterial-venous O2 saturation difference. O2 extraction and consumption were unaffected. The brain O2 supply/consumption ratio was maintained during hypoxic-hypocapnia indicating adequate and uniform protection in this condition throughout the brain.

Animals↗

Effect of stimulation of ansa subclavia on regional myocardial O2 supply and O2 consumption.

Cardiac sympathetic nerve stimulation produces increases in various indices of cardiac work and metabolism. To determine how these increased O2 demands are met, the effects of stimulation of the ansa subclavia on regional arterial and venous O2 saturation, O2 extraction, blood flow, and O2 consumption were determined in the hearts of 16 pentobarbital-anesthetized open-chest dogs. Microspectrophotometric observations of small regional arteries and veins in quick-frozen hearts to determine regional O2 extraction were combined with regional blood flow measurements with radioactive microspheres to determine regional myocardial O2 consumption by the Fick principle. Ansa subclavia stimulation produced significant increases in maximum rate of pressure development, heart rate, and blood pressure. Under control conditions, venous O2 saturation was lower and O2 extraction higher in the subendocardial compared with the subepicardial region of the left ventricle. While sympathetic stimulation did not alter the mean O2 extraction or venous O2 saturation values, there were no longer significant subepicardial vs. subendocardial differences in these parameters. Flow and O2 consumption in these regions increased proportionally during stimulation. The ratio of O2 supply to O2 consumption was not significantly altered by ansa subclavia stimulation, indicating that sympathetic stimulation produced no adverse effect in either region.

Animals↗

Thyroxine-induced hypertrophy of the rabbit heart. Effect on regional oxygen extraction, flow, and oxygen consumption.

The effects of the administration of 0.5 or 1 mg/kg of 1-thyroxine for 3 or 16 days were studied in 55 New Zealand white rabbits. Heart size was 29% above control after 16 days of 1-thyroxine, despite lower body weights. In an anesthetized open-chest animal, regional microspectro-photometric observations of small arteries and veins to determine oxygen extraction were combined with regional blood flow measurements using radioactive microspheres to determine regional oxygen consumption by the Fick principle. Vascular flow reserves were studied through measurement of blood flow after the administration of chromonar HCl, 10 mg/kg. Myocardial oxygen consumption was, respectively, 2.4 and 3.8 times control after 3 and 16 days of 1-thyroxine. This was accompanied by significant increases in both coronary blood flow and oxygen extraction. In control, oxygen extraction and consumption were higher in the subendocardial region compared to the subepicardial area. No significant regional differences were found in flow, oxygen extraction, or consumption after 1-thyroxine administration. Chromonar increased coronary blood flow 2.8 times in the control animals, but did not significantly increase flow or decrease vascular resistance in the rabbits given 1-thyroxine. Adenosine increased coronary blood flow 3.5 times in the control animals but only 2.2 times in animals given 1-thyroxine for 3 days. Animals given 1-thyroxine had hypertrophied hearts with increased oxygen consumption, markedly increased flow, and increased oxygen extraction but without regional left ventricular differences.

Animals↗

Microregional blood flow and high energy phosphates under conditions of high O2 supply in left ventricular subendocardium.

Blood flow and high energy phosphate (HEP) content were determined simultaneously in multiple microregions of the left ventricular subendocardium in 49 anaesthetized open-chest rabbits, to determine the relationship between the parameters during high O2 supply with hypercapnia and chromonar treatment. ATP and CP content were quantitated in quick-frozen hearts by fluorometry in 1-2 mg sites where perfusion was measured by H2 clearance employing bare-tipped platinum electrodes. Both hypercapnia and chromonar elevated subendocardial tissue perfusion approximately 30% and O2 supply 45% above control. Blood flow was normally distributed with either treatment, but was more homogeneous with hypercapnia. Neither treatment altered absolute levels of either HEP, but the variance of ATP was less than control. CP distribution was normal in both treatments. There was no significant linear correlation between blood flow and HEP under hypercapnia or chromonar treatment. We conclude that tissue HEP content is a variable not only dependent on O2 supply and blood flow, but also on the size of the ATP and CP pool and the energy demand of the local microregion. The variability of ATP in microregions of the rabbit subendocardium is reduced under conditions of high O2 supply.

Adenosine Triphosphate↗

Role of beta-1 adrenergic receptors in the control of the heterogeneity of O2 saturation in small myocardial veins.

The role of beta adrenergic receptors in the control of venous O2 saturation heterogeneity was studied in the left ventricular free wall of 24 anesthetized open-chest dogs. Venous and arterial O2 saturation was obtained microspectrophotometrically and combined with radioactive microsphere blood flow determinations to calculate regional myocardial O2 consumption. The mean and variance of venous O2 saturation were determined under six experimental conditions designed to produce graded levels of beta adrenergic activity. Regional O2 consumption, extraction and flow were also determined. Propranolol, 2 mg/kg, significantly lowered the O2 saturation variance in both small subepicardial and subendocardial veins compared to control. Isoproterenol, 10 micrograms/kg/min, did not alter the variance of venous O2 saturation. Isoproterenol, 10 micrograms/kg/min, in the presence of 2 mg/kg of propranolol was able to prevent the reduction in variance of venous O2 saturation seen with propropranolol alone. However, 0.1 microgram/kg/min of isoproterenol did not prevent this fall in venous O2 saturation variance with propranolol. Practolol, 1 mg/kg, also caused a significant fall in venous O2 saturation variance in the subepicardium and subendocardium. From this it can be concluded that there is an inhomogeneous distribution in beta-1 adrenergic receptor population and/or activity in the left ventricle. Thus, there appear to be small regions in the heart with high O2 consumption and extraction related to beta-1 adrenergic activity and/or distribution.

Animals↗

Effect of naltrexone on regional brain oxygen consumption in the cat.

Cerebral blood flow was measured by 141Ce and 85Sr microsphere accumulation, and oxygen saturation of arterial and venous blood within 9 regions of the brain was determined by microspectrophotometric measurement in chloralose anesthetized cats. Extraction was calculated as the difference between oxygen content of arterial and venous blood. Oxygen consumption was computed as the product of blood flow and oxygen extraction. Global and regional comparisons were made between 7 anesthetized cats and 7 anesthetized cats given 1 mg/kg naltrexone HCl i.v. Naltrexone treatment reduced total brain oxygen consumption by 48% at 20 min after intravenous injection. Analysis of the anterior and posterior cortex, lenticulate nuclei, hippocampus, thalamus, hypothalamus, medulla, pons and cerebellum indicated that the oxygen consumption of the pons and hypothalamus was reduced to the greatest extent. The decreased oxygen consumption reduced blood flow in the whole brain, and the pons. The oxygen supply to consumption ratio was not altered by naltrexone except in the hypothalamus where an even greater excess of oxygen was delivered. These observations are interpreted as indicating that opiate receptor blockade is associated with reduced brain metabolism and that this response is not restricted to regions of high opiate receptor concentration.

Animals↗

The effects of atrial fibrillation on atrial pressure-volume and flow relationships.

To study whether atrial fibrillation might produce local changes in the atrium which could facilitate the tendency of this arrhythmia to become chronic and self-perpetuating, we compared the effect of atrial fibrillation, atrial pacing, and acute volume loading on the perfusion and oxygen consumption of the atrium in anesthetized dogs. Measurement of atrial perfusion with microspheres indicates that during atrial fibrillation, atrial blood flow increases 2- to 3-fold. Right atrial pacing is a significantly less potent metabolic stimulus for atrial vasodilation. Using Doppler velocity recordings of sinus node artery blood flow velocity, a marked increase in velocity is observed within 5 seconds after the initiation of atrial fibrillation. During atrial fibrillation, the sinus node artery reactive hyperemia response is markedly attenuated. Atrial fibrillation acutely decreases atrial distensibility; atrial pressure increased 81 +/- 19% with only a small increase (9.7 +/- 3%) in atrial diameter measured by echocardiography. During sinus rhythm, volume expansion to equivalent levels of atrial pressure as seen during atrial fibrillation increased atrial diameter 21 +/- 5% P less than 0.05. Atrial oxygen consumption determined by the microspectrophotometric method markedly increases during atrial fibrillation, compared to control conditions (12.3 +/- 2.8 vs. 3.9 +/- 0.6 ml O2/min per 100 g, respectively) P less than 0.05. Atrial O2 extraction was 5.5 +/- 0.4 ml O2/ml blood in the control state, and did not change with interventions. There was a linear relationship between left atrial O2 consumption and blood flow in all experimental conditions. Atrial fibrillation therefore alters atrial hemodynamics and metabolism by increasing atrial blood flow and oxygen consumption and decreasing atrial distensibility. Since atrial perfusion during atrial fibrillation is high and atrial flow reserve is limited, it is possible that additional atrial metabolic requirements might lead to atrial ischemia, fibrosis, and, thereby, perpetuation of the arrhythmia.

Animals↗

Role of propranolol in improvement of the relationship between O2 supply and consumption in an ischemic region of the dog heart.

Several aspects of the myocardial O(2) supply/consumption relationship were determined after coronary artery occlusion and subsequent beta-adrenergic blockade in 16 anesthetized open-chest dogs. Small artery and vein O(2) saturations, and hence extraction, were obtained microspectrophotometrically and combined with radioactive microsphere blood flow determinations to calculate regional myocardial O(2) consumption. Eight dogs remained untreated after coronary artery ligation while another group was given 2 mg/kg propranolol, 10 min after occlusion. Untreated occlusion resulted in decreased arterial and especially venous O(2) saturations, indicating an increased O(2) extraction. Ischemic O(2) consumption was reduced and the subendocardial/subepicardial consumption ratio was reversed (1.26 vs. 0.37) due to the pattern of occluded area flow. Calculated O(2) supply/consumption also decreased. Propranolol produced no significant changes in volume or distribution of flow within the ischemic region while reducing flow, extraction, and consumption in the unoccluded region. The heterogeneity of arterial and particularly venous O(2) saturations within the ischemic region decreased dramatically. Venous O(2) saturations were elevated relative to the control group resulting in a reduced O(2) extraction. The decrease in heterogeneity of arterial and venous O(2) saturations suggest that propranolol eliminates microregions of relatively high O(2) extraction, consumption, and/or a majority of vessels with extremely low flow. This leads to a significant improvement in the O(2) supply/consumption ratio in the ischemic myocardium of the dog. This may be due to a reduction in the heterogeneity and level of beta(1)-adrenergic receptor activity within the heart.

Animals↗

Effects of phenoxybenzamine or N-methyl chlorpromazine on regional cerebral blood flow: comparison of central and peripheral alpha adrenergic receptor antagonism.

A comparison of the central and peripheral effects of alpha adrenergic receptor antagonism on regional cerebral blood flow was examined utilizing N-methyl chlorpromazine, an alpha adrenergic receptor antagonist which does not cross the blood-brain barrier, or phenoxybenzamine, an alpha adrenergic receptor antagonist which does enter the brain when injected systemically. Regional cerebral blood flow was monitored in 17 brain regions of 16 pentobarbital-anesthetized New Zealand White rabbits using radioactively tagged microspheres (15 +/- 3 micrometer in diameter). There was a significant overall difference in regional cerebral blood flow distribution in the control state. Although phenoxybenzamine had no significant effect on average global cerebral blood flow, this agent significantly redistributed flow among the various regions. Flow was significantly decreased in some cortical regions, the hippocampus and cerebellum, whereas flow was increased in the pons and substantia nigra. There were no significant effects of N-methyl chloropromazine on average global cerebral blood flow or its regional distribution. Central alpha adrenergic receptor blockade probably decreased regional cerebral blood flow in brain regions rich in neuronal alpha adrenoreceptors by decreasing regional metabolic and/or neuronal activity, while increasing metabolic and/or neuronal activity in the pons and substantia nigra via a positive feedback mechanism causing an increased flow rate in these regions. Peripheral alpha adrenergic receptor blockade appears to have little or no effect on regional cerebral blood flow.

Animals↗

Effect of moderate arterio-venous shunt on regional extraction, blood flow and oxygen consumption in the dog heart.

The effects of a moderate sized arterio-venous shunt on the relationship of oxygen supply to consumption were studied on a regional basis in the dog left ventricle. Experiments were conducted on fourteen hearts, seven in control pentobarbital-anaesthetised, open-chest dogs and seven in dogs with an additional abdominal aorto-caval shunt. Regional oxygen extraction was determined by a microspectrophotometric method and coronary blood flow was measured with radioactive microspheres. The shunt, when opened, allowed cardiac output to increase by 50%. This was accomplished by increasing stroke volume, not heart rate. In control animals the subendocardium exhibited higher oxygen extraction, coronary flow, and oxygen consumption than did the subepicardium. There were no differences between base and apex. In open-shunt animals, subepicardial-subendocardial differences in extraction, flow and consumption were abolished. Subepicardial values for these in shunt animals were not different from the values obtained for the subepicardial values of controls. The subendocardium of shunt animals exhibited significant differences between base and apex for blood flow and oxygen consumption. There was a significant difference in subendocardial oxygen consumption between groups, the effect of the arterio-venous shunt being to reduce subendocardial consumption, especially in the apex, without reducing subepicardial oxygen consumption.

Animals↗

Regional O2 consumption in canine left ventricular myocardium in experimental acute aortic valvular insufficiency.

Moderate and severe acute aortic valvular insufficiency (AVI) were produced for 30 min in anesthetised, open-chest dogs, in order to measure O2 consumption in subepicardial (EPI) and subendocardial (ENDO) regions of the left ventricular free wall. Regional O2 consumption (MVO2) was determined from regional O2 extraction and blood flow data determined by absorbence microspectrophotometry and radioactive microspheres. In all groups, venous saturations were lower and O2 extractions higher in the ENDO than in the EPI. Oxygen extractions increased in both regions in both severities of AVI, but more so with severe AVI. The ENDO became perfused relative to the EPI with increasing severity of AVI. Left ventricular MVO2 increased with AVI; however, ENDO MVO2 increased less than EPI MVO2. ENDO/EPI blood flow ratios decreased from 1.21 to 0.93 in moderate AVI and to 0.76 in severe AVI. ENDO/EPI MVO2 ratio decreased from 1.44 in controls to 0.94 in moderate and 0.54 in severe AVI. The ENDO/EPI MVO2 ratios began to decrease when DPTI/SPTI was less than 0.4 to 0.5. We conclude that AVI increases MVO2, but the ENDO cannot maintain its MVO2 relative to EPI because of proportionately less ENDO flow, and maximal O2 extraction.

Acute Disease↗

Blood flow and high-energy phosphates in microregions of left ventricular subendocardium.

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

Adenosine Triphosphate↗

Regional oxygen consumption and supply in heart: effect of methoxamine-induced pressure rise.

The effect of raising arterial blood pressure 50 mmHg with methoxamine on regional left ventricular O2 supply and consumption was studied in 27 pentobarbital-anesthetized open-chest rabbits. Three groups of animals were studied: 1) control, 2) methoxamine infusion sufficient to raise pressure 50 mmHg, and 3) methoxamine infusion sufficient to raise pressure 50 mmHg with atrial pacing to maintain heart rate. Subepicardial (epi) and subendocardial (endo) O2 saturations were determined with a microspectrophotometric technique. Regional flow was determined with radioactive microspheres and regional O2 consumption by the Fick principle. In the control group, endo venous O2 saturation [31 +/- 3% (SE)] was lower than epi (42 +/- 2%). There were no significant regional differences in blood flow (avg 128 +/- 2 ml . min-1 . 100 g-1). With methoxamine when heart rate fell, there were no differences in regional flow or consumption when compared to control. During methoxamine infusion, when heart rate was maintained, there was higher coronary blood flow (361 +/- 52 ml . min-1 . 100 g-1) and O2 consumption (27 +/- 4 ml O2 . min-1 . 100 g-1). No regional differences, epi vs. endo, were found in this group. After a 50-mmHg pressure rise, the endo region of the left ventricle had an increased O2 consumption mediated by an increased coronary blood flow without a significant rise in O2 extraction, similarly to epi.

Animals↗

Effect of papaverine on regional cerebral blood flow and small vessel blood content.

The effect of intravenous infusion of papaverine HCl, (2.0-2.5 mg/kg) on regional cerebral blood flow and small vessel blood content in anesthetized rats was determined. Cerebral blood flow was measured in the cerebral cortex, diencephalon plus midbrain, cerebellum, pons and medulla by means of the uptake of iodo[14C]antipyrine. Small vessel blood content was determined by labelling the plasma siderophilin with 59FeCl3. Cerebral blood flow showed interregional variation under control conditions. Papaverine increased flow in all regions, but the effect was greater in the hind compared to the forebrain. Papaverine did not significantly alter small vessel blood content or calculated open capillary density, indicating it had no functional effect upon cerebral precapillary sphincters, and therefore only affected cerebral arterioles.

Animals↗

Cerebral regional oxygen consumption and supply in anesthetized cat.

The study involved quantitative measurement of arterial and venous oxygen saturation, oxygen extraction, blood flow, and oxygen consumption in specific areas of the brain. No regional differences in oxygen consumption were found in anesthetized cat brain, and the amount of oxygen available to all regions studied was more than 2.5 times the consumption throughout the brain.

Anesthesia, General↗

Effects of carbon monoxide or low oxygen gas mixture inhalation on regional oxygenation, blood flow, and small vessel blood content of the rabbit heart.

The effects of lowering arterial O2 content, approximately 30%, by inspiration of low O2 or CO gas mixtures on regional myocardial relative tissue PO2, perfusion and small vessel blood content were studied in anesthetized, thoracotomized New Zealand white rabbits. Relative tissue PO2 and perfusion were determined polarographically. 59FeCl3 was used to determine small vessel blood content. In control, relative tissue PO2, perfusion and small vessel blood content averaged 33.1 mm Hg, 64.9 ml/min/100 g and 4.3 ml/100 g respectively in the subepicardium (EPI) and 22.7, 53.6 and 4.2 in the subendocardium (ENDO) of the left ventricle. Both hypoxic conditions increased regional blood flow, but to a lesser extent in the ENDO. Relative ENDO tissue PO2 fell more markedly than EPI in both conditions. Small vessel blood content increased more with CO than low O2. Regional O2 consumption, calculated by Krogh analysis, increased under both conditions. The response to lowered O2 content is thus an increase in flow, metabolic rate and the number of open capillaries with a lowered driving pressure for O2. The effects of these types of hypoxia appear more severe in the ENDO.

Animals↗